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Here, we review the molecular mechanisms that regulate the movement of glucose from the capillary bed into the muscle cell and discuss what is known about their integrated regulation during exercise. Novel developments within the field of mass spectrometry-based proteomics indicate that the known regulators of glucose uptake are only the tip of the iceberg.
Consequently, many exciting discoveries clearly lie ahead. This is a preview of subscription content, access via your institution. Wasserman, D. Four grams of glucose. Article CAS PubMed Google Scholar. Hoffman, N. et al. Global phosphoproteomic analysis of human skeletal muscle reveals a network of exercise-regulated kinases and AMPK substrates.
Cell Metab. Article CAS PubMed PubMed Central Google Scholar. Jensen, T. Jordy, A. Regulation of exercise-induced lipid metabolism in skeletal muscle. Regulation of glucose and glycogen metabolism during and after exercise.
Richter, E. Exercise, GLUT4, and skeletal muscle glucose uptake. van Loon, L. The effects of increasing exercise intensity on muscle fuel utilisation in humans. Romijn, J.
Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration. CAS PubMed Google Scholar. Ahlborg, G.
Substrate turnover during prolonged exercise in man. Splanchinc and leg metabolism of glucose, free fatty acids and amino acids. Coyle, E. Carbohydrate feeding during prolonged strenuous exercise can delay fatigue. Wahren, J.
Glucose metabolism during leg exercise in man. Katz, A. Leg glucose uptake during maximal dynamic exercise in humans. Ploug, T. Increased muscle glucose uptake during contractions: no need for insulin.
Wojtaszewski, J. Exercise modulates postreceptor insulin signaling and glucose transport in muscle-specific insulin receptor knockout mice.
Sakamoto, K. Role of Akt2 in contraction-stimulated cell signaling and glucose uptake in skeletal muscle. Minuk, H. Glucoregulatory and metabolic response to exercise in obese noninsulin-dependent diabetes.
Effect of exercise on insulin action in human skeletal muscle. Muscle glucose metabolism following exercise in the rat. Bogardus, C. Effect of muscle glycogen depletion on in vivo insulin action in man. Mikines, K. Effect of physical exercise on sensitivity and responsiveness to insulin in humans.
Devlin, J. Effects of prior high-intensity exercise on glucose metabolism in normal and insulin-resistant men. Diabetes 34— Boule, N. Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical trials.
JAMA— Fatone, C. Two weekly sessions of combined aerobic and resistance exercise are sufficient to provide beneficial effects in subjects with type 2 diabetes mellitus and metabolic syndrome. Dela, F. Effect of training on insulin-mediated glucose uptake in human muscle. Insulin-stimulated muscle glucose clearance in patients with NIDDM.
Effects of one-legged physical training. Diabetes 44— Knowler, W. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. Kjaer, M. Influence of active muscle mass on glucose homeostasis during exercise in humans.
Calbet, J. Central and peripheral hemodynamics in exercising humans: leg versus arm exercise. Sports 25 Suppl. Article PubMed Google Scholar. Joyner, M. Regulation of increased blood flow hyperemia to muscles during exercise: a hierarchy of competing physiological needs.
Mackie, B. Influence of training on blood flow to different skeletal muscle fiber types. Laughlin, M. Muscular blood flow distribution patterns as a function of running speed in rats.
Hellsten, Y. Vasodilator interactions in skeletal muscle blood flow regulation. Osorio-Fuentealba, C. Electrical stimuli release ATP to increase GLUT4 translocation and glucose uptake via PI3Kγ-Akt-AS in skeletal muscle cells.
Diabetes 62— Vincent, M. Mixed meal and light exercise each recruit muscle capillaries in healthy humans. Sjoberg, K. A new method to study changes in microvascular blood volume in muscle and adipose tissue: real-time imaging in humans and rat. Heart Circ. Article PubMed CAS Google Scholar.
MacLean, D.
: Exercise and glucose metabolism| Glucose metabolism during leg exercise in man | J Diabetes Res. Article CAS Google Scholar Yeo, W. The various metabolic pathways are regulated by a range of intramuscular and hormonal signals that influence enzyme activation and substrate availability, thus ensuring that the rate of ATP resynthesis is closely matched to the ATP demands of exercise. Hulston, C. Diabetologia 53 , — Appl Physiol Nutr Metab 34 1 —32 Article CAS PubMed Google Scholar Bruce CR, Dyck DJ Cytokine regulation of skeletal muscle fatty acid metabolism: effect of interleukin-6 and tumor necrosis factor-α. Nature , — |
| Glucose uptake through physical exercise | Some decades later, Lawrenceshowed that physical exercise could enhance the effects of the hormone insulin, resulting in increased glucose consumption and internalization, suggesting that physical exercise could be relevant for the treatment of diabetic people 2 2 Lawrence RD. Given that liver glucose uptake and glycogen synthesis correspond well with one another 78 , it is not surprising that a number of studies have demonstrated diminished SGU in patients with T2D. Jorgensen, S. Török D, Patel N, Jebailey L, Thong FSL, Randhawa VK, Klip A, et al. Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve, Belgium. Article CAS PubMed PubMed Central Google Scholar Witczak, C. |
| 3 Ways Exercise Can Promote Glucose Metabolism | Santa Cruz CORE Fitness + Rehab | Exefcise proteins for fat are blucose translocated to the muscle ans mainly Metaboolism membrane fatty acid—binding protein and mitochondrial membranes mainly fatty Exercise and glucose metabolism translocase FAT, also Boosting collagen production as CD36 glicose, where they transport fatty acids into cells and mitochondria 59 About this article. Most notably, it would be of particular benefit to know the individual and interactive effects of exercise training and weight loss on SGU. A few years before the description of AMPK activation by physical exercise and related experimental evidence in humans, animal researches identified a drug compound known to act as a potent activator of this molecule, AICAR 5-aminoimidazole ribonucleotidecarboxamide. Diabetes Metab Syndr Obes Targets Ther Ørtenblad, N. Regulation of endogenous glucose production after a mixed meal in type 2 diabetes. |
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What happens to your blood sugar when you work out? Type 2 diabetes T2D is a metabolic disease characterized by Exercise and glucose metabolism, Citrus aurantium for immune support resistance, and the dysfunction of several Eercise glucoregulatory organs. Metaboljsm these organs, impaired metanolism function is recognized Exegcise one of the earliest glycose to metabo,ism whole-body glucose homeostasis, Refillable beauty products well-characterized hepatic insulin resistance resulting Exegcise elevated rates of hepatic glucose production HGP and fasting Exerciise. One portion of xnd review andd provide an overview of how HGP is regulated during the fasted state in healthy humans and how this process becomes dysregulated in patients with T2D. Less well-appreciated is the liver's role in post-prandial glucose metabolism, where it takes up and metabolizes one-third of orally ingested glucose. An abundance of literature has shown that the process of hepatic glucose uptake is impaired in patients with T2D, thereby contributing to glucose intolerance. A second portion of this review will outline how hepatic glucose uptake is regulated during the post-prandial state, and how it becomes dysfunctional in patients with T2D. Finally, it is well-known that exercise training has an insulin-sensitizing effect on the liver, which contributes to improved whole-body glucose metabolism in patients with T2D, thereby making it a cornerstone in the management of the disease.
Exercise and glucose metabolism -
Another area that has been investigated is the effects of menstrual phase and menstrual status on the regulation of skeletal muscle metabolism.
Generally, studies examining exercise in the luteal and follicular phases have reported only minor or no changes in fat and carbohydrate metabolism at various exercise intensities , , , Additional work examining the regulation of metabolism in well-trained female participants in both phases of the menstrual cycle, and with varied menstrual cycles, during exercise at the high aerobic and supramaximal intensities commensurate with elite sports, is warranted.
Sports performance is determined by many factors but is ultimately limited by the development of fatigue, such that the athletes with the greatest fatigue resistance often succeed. However, there can be a fine line between glory and catastrophe, and the same motivation that drives athletes to victory can at times push them beyond their limits.
Fatigue is the result of a complex interplay among central neural regulation, neuromuscular function and the various physiological processes that support skeletal muscle performance 1.
It manifests as a decrease in the force or power-producing capacity of skeletal muscle and an inability to maintain the exercise intensity needed for ultimate success.
Over the years, considerable interest has been placed on the relative importance of central neural and peripheral muscle factors in the aetiology of fatigue.
All that I am, I am because of my mind. Perhaps the two major interventions used to enhance fatigue resistance are regular training and nutrition 70 , and the interactions between them have been recognized We briefly review the effects of training and nutrition on skeletal muscle energy metabolism and exercise performance, with a focus on substrate availability and metabolic end products.
In relation to dietary supplements, we have limited our discussion to those that have been reasonably investigated for efficacy in human participants Regular physical training is an effective strategy for enhancing fatigue resistance and exercise performance, and many of these adaptations are mediated by changes in muscle metabolism and morphology.
Such training is also associated with the cardiovascular and metabolic benefits often observed with traditional endurance training One hallmark adaptation to endurance exercise training is increased oxygen-transport capacity, as measured by VO 2 max 78 , thus leading to greater fatigue resistance and enhanced exercise performance The other is enhanced skeletal muscle mitochondrial density 80 , a major factor contributing to decreased carbohydrate utilization and oxidation and lactate production 81 , 82 , increased fat oxidation and enhanced endurance exercise performance The capacity for muscle carbohydrate oxidation also increases, thereby enabling maintenance of a higher power output during exercise and enhanced performance Finally, resistance training results in increased strength, neuromuscular function and muscle mass 85 , effects that can be potentiated by nutritional interventions, such as increased dietary protein intake The improved performance is believed to be due to enhanced ATP resynthesis during exercise as a result of increased PCr availability.
Some evidence also indicates that creatine supplementation may increase muscle mass and strength during resistance training No major adverse effects of creatine supplementation have been observed in the short term, but long-term studies are lacking.
Creatine remains one of the most widely used sports-related dietary supplements. The importance of carbohydrate for performance in strenuous exercise has been recognized since the early nineteenth century, and for more than 50 years, fatigue during prolonged strenuous exercise has been associated with muscle glycogen depletion 13 , Muscle glycogen is critical for ATP generation and supply to all the key ATPases involved in excitation—contraction coupling in skeletal muscle Recently, prolonged exercise has been shown to decrease glycogen in rodent brains, thus suggesting the intriguing possibility that brain glycogen depletion may contribute to central neural fatigue Muscle glycogen availability may also be important for high-intensity exercise performance Blood glucose levels decline during prolonged strenuous exercise, because the liver glycogen is depleted, and increased liver gluconeogenesis is unable to generate glucose at a rate sufficient to match skeletal muscle glucose uptake.
Maintenance of blood glucose levels at or slightly above pre-exercise levels by carbohydrate supplementation maintains carbohydrate oxidation, improves muscle energy balance at a time when muscle glycogen levels are decreased and delays fatigue 20 , 97 , Glucose ingestion during exercise has minimal effects on net muscle glycogen utilization 97 , 99 , but increases muscle glucose uptake and markedly decreases liver glucose output , , because the gut provides most glucose to the bloodstream.
Importantly, although carbohydrate ingestion delays fatigue, it does not prevent fatigue, and many factors clearly contribute to fatigue during prolonged strenuous exercise. Because glucose is the key substrate for the brain, central neural fatigue may develop during prolonged exercise as a consequence of hypoglycaemia and decreased cerebral glucose uptake Carbohydrate ingestion exerts its benefit by increasing cerebral glucose uptake and maintaining central neural drive NH 3 can cross the blood—brain barrier and has the potential to affect central neurotransmitter levels and central neural fatigue.
Of note, carbohydrate ingestion attenuates muscle and plasma NH 3 accumulation during exercise , another potential mechanism through which carbohydrate ingestion exerts its ergogenic effect.
Enhanced exercise performance has also been observed from simply having carbohydrate in the mouth, an effect that has been linked to activation of brain centres involved in motor control Increased plasma fatty acid availability decreases muscle glycogen utilization and carbohydrate oxidation during exercise , , High-fat diets have also been proposed as a strategy to decrease reliance on carbohydrate and improve endurance performance.
Other studies have demonstrated increased fat oxidation and lower rates of muscle glycogen use and carbohydrate oxidation after adaptation to a short-term high-fat diet, even with restoration of muscle glycogen levels, but no effect on endurance exercise performance , If anything, high-intensity exercise performance is impaired on the high-fat diet , apparently as a result of an inability to fully activate glycogenolysis and PDH during intense exercise Furthermore, a high-fat diet has been shown to impair exercise economy and performance in elite race walkers A related issue with high-fat, low carbohydrate diets is the induction of nutritional ketosis after 2—3 weeks.
However, when this diet is adhered to for 3 weeks, and the concentrations of ketone bodies are elevated, a decrease in performance has been observed in elite race walkers The rationale for following this dietary approach to optimize performance has been called into question Although training on a high-fat diet appears to result in suboptimal adaptations in previously untrained participants , some studies have reported enhanced responses to training with low carbohydrate availability in well-trained participants , Over the years, endurance athletes have commonly undertaken some of their training in a relatively low-carbohydrate state.
However, maintaining an intense training program is difficult without adequate dietary carbohydrate intake Furthermore, given the heavy dependence on carbohydrate during many of the events at the Olympics 9 , the most effective strategy for competition would appear to be one that maximizes carbohydrate availability and utilization.
Nutritional ketosis can also be induced by the acute ingestion of ketone esters, which has been suggested to alter fuel preference and enhance performance The metabolic state induced is different from diet-induced ketosis and has the potential to alter the use of fat and carbohydrate as fuels during exercise.
However, published studies on trained male athletes from at least four independent laboratories to date do not support an increase in performance.
Acute ingestion of ketone esters has been found to have no effect on 5-km and km trial performance , , or performance during an incremental cycling ergometer test A further study has reported that ketone ester ingestion decreases performance during a The rate of ketone provision and metabolism in skeletal muscle during high-intensity exercise appears likely to be insufficient to substitute for the rate at which carbohydrate can provide energy.
Early work on the ingestion of high doses of caffeine 6—9 mg caffeine per kg body mass 60 min before exercise has indicated enhanced lipolysis and fat oxidation during exercise, decreased muscle glycogen use and increased endurance performance in some individuals , , These effects appear to be a result of caffeine-induced increases in catecholamines, which increase lipolysis and consequently fatty acid concentrations during the rest period before exercise.
After exercise onset, these circulating fatty acids are quickly taken up by the tissues of the body 10—15 min , fatty acid concentrations return to normal, and no increases in fat oxidation are apparent. Importantly, the ergogenic effects of caffeine have also been reported at lower caffeine doses ~3 mg per kg body mass during exercise and are not associated with increased catecholamine and fatty acid concentrations and other physiological alterations during exercise , This observation suggests that the ergogenic effects are mediated not through metabolic events but through binding to adenosine receptors in the central and peripheral nervous systems.
Caffeine has been proposed to increase self-sustained firing, as well as voluntary activation and maximal force in the central nervous system, and to decrease the sensations associated with force, pain and perceived exertion or effort during exercise in the peripheral nervous system , The ingestion of low doses of caffeine is also associated with fewer or none of the adverse effects reported with high caffeine doses anxiety, jitters, insomnia, inability to focus, gastrointestinal unrest or irritability.
Contemporary caffeine research is focusing on the ergogenic effects of low doses of caffeine ingested before and during exercise in many forms coffee, capsules, gum, bars or gels , and a dose of ~ mg caffeine has been argued to be optimal for exercise performance , The potential of supplementation with l -carnitine has received much interest, because this compound has a major role in moving fatty acids across the mitochondrial membrane and regulating the amount of acetyl-CoA in the mitochondria.
The need for supplemental carnitine assumes that a shortage occurs during exercise, during which fat is used as a fuel. Although this outcome does not appear to occur during low-intensity and moderate-intensity exercise, free carnitine levels are low in high-intensity exercise and may contribute to the downregulation of fat oxidation at these intensities.
However, oral supplementation with carnitine alone leads to only small increases in plasma carnitine levels and does not increase the muscle carnitine content An insulin level of ~70 mU l —1 is required to promote carnitine uptake by the muscle However, to date, there is no evidence that carnitine supplementation can improve performance during the higher exercise intensities common to endurance sports.
NO is an important bioactive molecule with multiple physiological roles within the body. It is produced from l -arginine via the action of nitric oxide synthase and can also be formed by the nonenzymatic reduction of nitrate and nitrite.
The observation that dietary nitrate decreases the oxygen cost of exercise has stimulated interest in the potential of nitrate, often ingested in the form of beetroot juice, as an ergogenic aid during exercise.
Indeed, several studies have observed enhanced exercise performance associated with lower oxygen cost and increased muscle efficiency after beetroot-juice ingestion , , The effect of nitrate supplementation appears to be less apparent in well-trained athletes , , although results in the literature are varied Dietary nitrate supplementation may have beneficial effects through an improvement in excitation—contraction coupling , , because supplementation with beetroot juice does not alter mitochondrial efficiency in human skeletal muscle , and the results with inorganic nitrate supplementation have been equivocal , Lactate is not thought to have a major negative effect on force and power generation and, as mentioned earlier, is an important metabolic intermediate and signalling molecule.
Of greater importance is the acidosis arising from increased muscle metabolism and strong ion fluxes. In humans, acidosis does not appear to impair maximal isometric-force production, but it does limit the ability to maintain submaximal force output , thus suggesting an effect on energy metabolism and ATP generation Ingestion of oral alkalizers, such as bicarbonate, is often associated with increased high-intensity exercise performance , , partly because of improved energy metabolism and ionic regulation , As previously mentioned, high-intensity exercise training increases muscle buffer capacity 74 , A major determinant of the muscle buffering capacity is carnosine content, which is higher in sprinters and rowers than in marathon runners or untrained individuals Ingestion of β-alanine increases muscle carnosine content and enhances high-intensity exercise performance , During exercise, ROS, such as superoxide anions, hydrogen peroxide and hydroxyl radicals, are produced and have important roles as signalling molecules mediating the acute and chronic responses to exercise However, ROS accumulation at higher levels can negatively affect muscle force and power production and induce fatigue 68 , Exercise training increases the levels of key antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase , and non-enzymatic antioxidants reduced glutathione, β-carotene, and vitamins C and E can counteract the negative effects of ROS.
Whether dietary antioxidant supplementation can improve exercise performance is equivocal , although ingestion of N -acetylcysteine enhances muscle oxidant capacity and attenuates muscle fatigue during prolonged exercise Some reports have suggested that antioxidant supplementation may potentially attenuate skeletal muscle adaptation to regular exercise , , Overall, ROS may have a key role in mediating adaptations to acute and chronic exercise but, when they accumulate during strenuous exercise, may exert fatigue effects that limit exercise performance.
The negative effects of hyperthermia are potentiated by sweating-induced fluid losses and dehydration , particularly decreased skeletal muscle blood flow and increased muscle glycogen utilization during exercise in heat Increased plasma catecholamines and elevated muscle temperatures also accelerate muscle glycogenolysis during exercise in heat , , Strategies to minimize the negative effects of hyperthermia on muscle metabolism and performance include acclimation, pre-exercise cooling and fluid ingestion , , , To meet the increased energy needs of exercise, skeletal muscle has a variety of metabolic pathways that produce ATP both anaerobically requiring no oxygen and aerobically.
These pathways are activated simultaneously from the onset of exercise to precisely meet the demands of a given exercise situation. Although the aerobic pathways are the default, dominant energy-producing pathways during endurance exercise, they require time seconds to minutes to fully activate, and the anaerobic systems rapidly in milliseconds to seconds provide energy to cover what the aerobic system cannot provide.
Anaerobic energy provision is also important in situations of high-intensity exercise, such as sprinting, in which the requirement for energy far exceeds the rate that the aerobic systems can provide. This situation is common in stop-and-go sports, in which transitions from lower-energy to higher-energy needs are numerous, and provision of both aerobic and anaerobic energy contributes energy for athletic success.
Together, the aerobic energy production using fat and carbohydrate as fuels and the anaerobic energy provision from PCr breakdown and carbohydrate use in the glycolytic pathway permit Olympic athletes to meet the high energy needs of particular events or sports.
The various metabolic pathways are regulated by a range of intramuscular and hormonal signals that influence enzyme activation and substrate availability, thus ensuring that the rate of ATP resynthesis is closely matched to the ATP demands of exercise.
Regular training and various nutritional interventions have been used to enhance fatigue resistance via modulation of substrate availability and the effects of metabolic end products. The understanding of exercise energy provision, the regulation of metabolism and the use of fat and carbohydrate fuels during exercise has increased over more than years, on the basis of studies using various methods including indirect calorimetry, tissue samples from contracting skeletal muscle, metabolic-tracer sampling, isolated skeletal muscle preparations, and analysis of whole-body and regional arteriovenous blood samples.
However, in virtually all areas of the regulation of fat and carbohydrate metabolism, much remains unknown. The introduction of molecular biology techniques has provided opportunities for further insights into the acute and chronic responses to exercise and their regulation, but even those studies are limited by the ability to repeatedly sample muscle in human participants to fully examine the varied time courses of key events.
The ability to fully translate findings from in vitro experiments and animal studies to exercising humans in competitive settings remains limited. The field also continues to struggle with measures specific to the various compartments that exist in the cell, and knowledge remains lacking regarding the physical structures and scaffolding inside these compartments, and the communication between proteins and metabolic pathways within compartments.
A clear example of these issues is in studying the events that occur in the mitochondria during exercise. One area that has not advanced as rapidly as needed is the ability to non-invasively measure the fuels, metabolites and proteins in the various important muscle cell compartments that are involved in regulating metabolism during exercise.
Although magnetic resonance spectroscopy has been able to measure certain compounds non-invasively, measuring changes that occur with exercise at the molecular and cellular levels is generally not possible.
Some researchers are investigating exercise metabolism at the whole-body level through a physiological approach, and others are examining the intricacies of cell signalling and molecular changes through a reductionist approach.
New opportunities exist for the integrated use of genomics, proteomics, metabolomics and systems biology approaches in data analyses, which should provide new insights into the molecular regulation of exercise metabolism.
Many questions remain in every area of energy metabolism, the regulation of fat and carbohydrate metabolism during exercise, optimal training interventions and the potential for manipulation of metabolic responses for ergogenic benefits. Exercise biology will thus continue to be a fruitful research area for many years as researchers seek a greater understanding of the metabolic bases for the athletic successes that will be enjoyed and celebrated during the quadrennial Olympic festival of sport.
Hawley, J. Integrative biology of exercise. Cell , — Article CAS PubMed Google Scholar. Sahlin, K. Energy supply and muscle fatigue in humans.
Acta Physiol. Medbø, J. Anaerobic energy release in working muscle during 30 s to 3 min of exhausting bicycling.
Article PubMed Google Scholar. Parolin, M. et al. Regulation of skeletal muscle glycogen phosphorylase and PDH during maximal intermittent exercise. CAS PubMed Google Scholar. Greenhaff, P.
The metabolic responses of human type I and II muscle fibres during maximal treadmill sprinting. Article Google Scholar. Relative importance of aerobic and anaerobic energy release during short-lasting exhausting bicycle exercise.
Tesch, P. Muscle metabolism during intense, heavy-resistance exercise. Koopman, R. Intramyocellular lipid and glycogen content are reduced following resistance exercise in untrained healthy males.
Carbohydrate dependence during prolonged, intense endurance exercise. Sports Med. Carbohydrate dependence during marathon running. Sports Exerc.
PubMed Google Scholar. Romijn, J. Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration. van Loon, L. The effects of increasing exercise intensity on muscle fuel utilisation in humans. Bergström, J. A study of the glycogen metabolism during exercise in man.
Wahren, J. Glucose metabolism during leg exercise in man. Article CAS PubMed PubMed Central Google Scholar. Ahlborg, G. Substrate turnover during prolonged exercise in man. Watt, M. Intramuscular triacylglycerol, glycogen and acetyl group metabolism during 4 h of moderate exercise in man.
Article CAS Google Scholar. Inhibition of adipose tissue lipolysis increases intramuscular lipid and glycogen use in vivo in humans. Article PubMed CAS Google Scholar. Wasserman, D. Four grams of glucose. Coggan, A. Effect of endurance training on hepatic glycogenolysis and gluconeogenesis during prolonged exercise in men.
Coyle, E. Carbohydrate feeding during prolonged strenuous exercise can delay fatigue. Horowitz, J. Lipid metabolism during endurance exercise.
Kiens, B. Skeletal muscle lipid metabolism in exercise and insulin resistance. Stellingwerff, T. Significant intramyocellular lipid use during prolonged cycling in endurance-trained males as assessed by three different methodologies.
Spriet, L. An enzymatic approach to lactate production in human skeletal muscle during exercise. Brooks, G. The lactate shuttle during exercise and recovery. Miller, B. Lactate and glucose interactions during rest and exercise in men: effect of exogenous lactate infusion.
Lactate elimination and glycogen resynthesis after intense bicycling. Hashimoto, T. Lactate sensitive transcription factor network in L6 cells: activation of MCT1 and mitochondrial biogenesis. FASEB J. Takahashi, H. TGF-β2 is an exercise-induced adipokine that regulates glucose and fatty acid metabolism.
Metab 1 , — Scheiman, J. Meta-omics analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism. Rennie, M. Effect of exercise on protein turnover in man.
Wagenmakers, A. Carbohydrate supplementation, glycogen depletion, and amino acid metabolism during exercise. Howarth, K. Effect of glycogen availability on human skeletal muscle protein turnover during exercise and recovery.
McKenzie, S. Endurance exercise training attenuates leucine oxidation and BCOAD activation during exercise in humans. Wilkinson, S. Differential effects of resistance and endurance exercise in the fed state on signalling molecule phosphorylation and protein synthesis in human muscle.
Egan, B. Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell Metab. New insights into the interaction of carbohydrate and fat metabolism during exercise.
Hargreaves, M. Exercise metabolism: fuels for the fire. Cold Spring Harb. Article PubMed PubMed Central CAS Google Scholar. Richter, E. Muscle glycogenolysis during exercise: dual control by epinephrine and contractions. Gaitanos, G.
Human muscle metabolism during intermittent maximal exercise. Kowalchuk, J. Factors influencing hydrogen ion concentration in muscle after intense exercise. Howlett, R. Regulation of skeletal muscle glycogen phosphorylase and PDH at varying exercise power outputs.
Wojtaszewski, J. Chen, Z. AMPK signaling in contracting human skeletal muscle: acetyl-CoA carboxylase and NO synthase phosphorylation.
Stephens, T. Progressive increase in human skeletal muscle AMPKα2 activity and ACC phosphorylation during exercise. Yu, M. Metabolic and mitogenic signal transduction in human skeletal muscle after intense cycling exercise. Rose, A. McConell, G. Hoffman, N. Global phosphoproteomic analysis of human skeletal muscle reveals a network of exercise-regulated kinases and AMPK substrates.
Nelson, M. Phosphoproteomics reveals conserved exercise-stimulated signaling and AMPK regulation of store-operated calcium entry. EMBO J. Needham, E. Phosphoproteomics of acute cell stressors targeting exercise signaling networks reveal drug interactions regulating protein secretion.
Cell Rep. e6 Perry, C. Mitochondrial creatine kinase activity and phosphate shuttling are acutely regulated by exercise in human skeletal muscle. Miotto, P. In the absence of phosphate shuttling, exercise reveals the in vivo importance of creatine-independent mitochondrial ADP transport.
Holloway, G. Nutrition and training influences on the regulation of mitochondrial adenosine diphosphate sensitivity and bioenergetics. Suppl 1. Article PubMed PubMed Central Google Scholar. Effects of dynamic exercise intensity on the activation of hormone-sensitive lipase in human skeletal muscle.
Talanian, J. Beta-adrenergic regulation of human skeletal muscle hormone sensitive lipase activity during exercise onset. CAS Google Scholar. Exercise, GLUT4, and skeletal muscle glucose uptake.
Sylow, L. Exercise-stimulated glucose uptake: regulation and implications for glycaemic control. Bradley, N. Acute endurance exercise increases plasma membrane fatty acid transport proteins in rat and human skeletal muscle.
Smith, B. Sport Sci. Petrick, H. High intensity exercise inhibits carnitine palmitoyltransferase-I sensitivity to L-carnitine. Krustrup, P. Muscle and blood metabolites during a soccer game: implications for sprint performance.
Achten, J. Maximal fat oxidation during exercise in trained men. Harris, R. The time course of phosphorylcreatine resynthesis during recovery of the quadriceps muscle in man. Pflugers Arch. Taylor, J. Neural contributions to muscle fatigue: from the brain to the muscle and back again.
Allen, D. Skeletal muscle fatigue: cellular mechanisms. Amann, M. Central and peripheral fatigue: interaction during cycling exercise in humans.
Burke, L. Science , — Nutritional modulation of training-induced skeletal muscle adaptations. Maughan, R. IOC consensus statement: dietary supplements and the high-performance athlete.
Roberts, A. Anaerobic muscle enzyme changes after interval training. Sharp, R. Effects of eight weeks of bicycle ergometer sprint training on human muscle buffer capacity. Weston, A. Skeletal muscle buffering capacity and endurance performance after high-intensity interval training by well-trained cyclists.
McKenna, M. Sprint training enhances ionic regulation during intense exercise in men. Gibala, M. Physiological adaptations to low-volume, high-intensity interval training in health and disease. Lundby, C. Biology of VO 2 max: looking under the physiology lamp. Convective oxygen transport and fatigue.
Holloszy, J. Adaptations of skeletal muscle to endurance exercise and their metabolic consequences. Chesley, A. Regulation of muscle glycogen phosphorylase activity following short-term endurance training. Leblanc, P. Randle P, Newsholme E, Garland P Regulation of glucose uptake by muscle.
Effects of fatty acids, ketone bodies and pyruvate, and of alloxan-diabetes and starvation, on the uptake and metabolic fate of glucose in rat heart and diaphragm muscles. Biochem J 93 3 Reiber GE, Boyko EJ, Smith DG Lower extremity foot ulcers and amputations in diabetes.
Diabetes Am — Richards JC, Johnson TK, Kuzma JN, Lonac MC, Schweder MM, Voyles WF, Bell C Short-term sprint interval training increases insulin sensitivity in healthy adults but does not affect the thermogenic response to β-adrenergic stimulation.
J Physiol 15 — Richter EA, Garetto LP, Goodman MN, Ruderman NB Muscle glucose metabolism following exercise in the rat: increased sensitivity to insulin. J Clin Investig 69 4 Richter EA, Cleland PJ, Rattigan S, Clark MG Contraction-associated translocation of protein kinase C in rat skeletal muscle.
FEBS Lett 2 — Richter EA, Derave W, Wojtaszewski JFP Glucose, exercise and insulin: emerging concepts. J Physiol 2 — Rizza RA, Mandarino LJ, Gerich JE Effects of growth hormone on insulin action in man: mechanisms of insulin resistance, impaired suppression of glucose production, and impaired stimulation of glucose utilization.
Diabetes 31 8 — Roberts S, Desbrow B, Grant G, Anoopkumar-Dukie S, Leveritt M Glycemic response to carbohydrate and the effects of exercise and protein. Nutrition 29 6 — Roden M, Shulman GI Applications of NMR spectroscopy to study muscle glycogen metabolism in man. Annu Rev Med — Röder PV, Wu B, Liu Y, Han W Pancreatic regulation of glucose homeostasis.
Exp Mol Med 48 3 :e—e Rose AJ, Howlett K, King DS, Hargreaves M Effect of prior exercise on glucose metabolism in trained men.
Proc Natl Acad Sci USA 95 3 — Rynders CA, Weltman JY, Jiang B, Breton M, Patrie J, Barrett EJ, Weltman A Effects of exercise intensity on postprandial improvement in glucose disposal and insulin sensitivity in prediabetic adults. J Clin Endocrinol Metab 99 1 — Sahlin K Metabolic factors in fatigue.
Sports Med 13 2 — Sakagami H, Makino Y, Mizumoto K, Isoe T, Takeda Y, Watanabe J, Fujita Y, Takiyama Y, Abiko A, Haneda M Loss of HIF-1α impairs GLUT4 translocation and glucose uptake by the skeletal muscle cells.
Am J Physiol Endocrinol Metab 9 :E—E Schmidt W, Dore S, Hilgendorf A, Strauch S, Gareau R, Brisson G Effects of exercise during normoxia and hypoxia on the growth hormone—insulin-like growth factor I axis.
Eur J Appl Physiol 71 5 — Scholz CC, Taylor CT Targeting the HIF pathway in inflammation and immunity. Curr Opin Pharmacol 13 4 — Schwarz J-M, Mulligan K, Lee J, Lo JC, Wen M, Noor MA, Grunfeld C, Schambelan M Effects of recombinant human growth hormone on hepatic lipid and carbohydrate metabolism in HIV-infected patients with fat accumulation.
J Clin Endocrinol Metab 87 2 — Segerlantz M, Bramnert M, Manhem P, Laurila E, Groop LC Inhibition of lipolysis during acute GH exposure increases insulin sensitivity in previously untreated GH-deficient adults. Eur J Endocrinol 6 — Semenza G Regulation of metabolism by hypoxia-inducible factor 1.
Cold Spring Harbor symposia on quantitative biology. Cold Spring Harbor Laboratory Press, pp — Semenza GL Hypoxia-inducible factors in physiology and medicine. Cell 3 — Shearer J, Graham TE Novel aspects of skeletal muscle glycogen and its regulation during rest and exercise.
Exerc Sport Sci Rev 32 3 — Sherwin RS, Shamoon H, Hendler R, Sacca L, Eigler N, Walesky M Epinephrine and the regulation of glucose metabolism: effect of diabetes and hormonal interactions. Metabolism 29 11 Suppl 1 — Smith TR, Elmendorf JS, David TS, Turinsky J Growth hormone-induced insulin resistance: role of the insulin receptor, IRS-1, GLUT-1, and GLUT Solomon TP, Haus JM, Kelly KR, Rocco M, Kashyap SR, Kirwan JP Improved pancreatic β-cell function in type 2 diabetic patients after lifestyle-induced weight loss is related to glucose-dependent insulinotropic polypeptide.
Diabetes Care 33 7 — Soo J, Girard O, Ihsan M, Fairchild T The use of the SpO2 to FiO2 ratio to individualize the hypoxic dose in sport science, exercise, and health settings. Stefan N, Wahl HG, Fritsche A, Haring H, Stumvoll M Effect of the pattern of elevated free fatty acids on insulin sensitivity and insulin secretion in healthy humans.
Horm Metab Res 33 7 — Stefan N, Staiger H, Wagner R, Machann J, Schick F, Häring H-U, Fritsche A A high-risk phenotype associates with reduced improvement in glycaemia during a lifestyle intervention in prediabetes.
Diabetologia 58 12 — Stuart CA, Yin D, Howell MEA, Dykes RJ, Laffan JJ, Ferrando AA Hexose transporter mRNAs for GLUT4, GLUT5, and GLUT12 predominate in human muscle.
Suhre K Metabolic profiling in diabetes. J Endocrinol 3 :R75—R Sun L, Liang L, Gao X, Zhang H, Yao P, Hu Y, Ma Y, Wang F, Jin Q, Li H Early prediction of developing type 2 diabetes by plasma acylcarnitines: a population-based study.
Diabetes Care 39 9 — Sutton JR Effect of acute hypoxia on the hormonal response to exercise. J Appl Physiol 42 4 — Svensson J, Fowelin J, Landin K, Bengtsson B-AK, Johansson J-O Effects of seven years of GH-replacement therapy on insulin sensitivity in GH-deficient adults.
J Clin Endocrinol Metab 87 5 — Sylow L, Jensen TE, Kleinert M, Mouatt JR, Maarbjerg SJ, Jeppesen J, Prats C, Chiu TT, Boguslavsky S, Klip A Rac1 is a novel regulator of contraction-stimulated glucose uptake in skeletal muscle. Diabetes 62 4 — Sylow L, Kleinert M, Richter EA, Jensen TE Exercise-stimulated glucose uptake—regulation and implications for glycaemic control.
Nat Rev Endocrinol 13 3 — Sylow L, Tokarz VL, Richter EA, Klip A The many actions of insulin in skeletal muscle, the paramount tissue determining glycemia. Cell Metab 33 4 — Tai E, Tan M, Stevens R, Low Y, Muehlbauer M, Goh D, Ilkayeva O, Wenner B, Bain J, Lee J Insulin resistance is associated with a metabolic profile of altered protein metabolism in Chinese and Asian—Indian men.
Diabetologia 53 4 — Takano A, Haruta T, Iwata M, Usui I, Uno T, Kawahara J, Ueno E, Sasaoka T, Kobayashi M Growth hormone induces cellular insulin resistance by uncoupling phosphatidylinositol 3-kinase and its downstream signals in 3T3-L1 adipocytes.
Diabetes 50 8 — Thomas D, Elliott EJ, Naughton GA Exercise for type 2 diabetes mellitus. Cochrane Database Syst Rev 3 3 :CD Trefts E, Williams AS, Wasserman DH Exercise and the regulation of hepatic metabolism. Prog Mol Biol Transl Sci — Tsukui S, Kanda T, Nara M, Nishino M, Kondo T, Kobayashi I Moderate-intensity regular exercise decreases serum tumor necrosis factor-alpha and HbA1c levels in healthy women.
Int J Obes Relat Metab Disord 24 9 — Umpierre D, Ribeiro PAB, Kramer CK, Leitao CB, Zucatti ATN, Azevedo MJ, Gross JL, Ribeiro JP, Schaan BD Physical activity advice only or structured exercise training and association with HbA 1c levels in type 2 diabetes A systematic review and meta-analysis.
JAMA J Am Med Assoc 17 — Umpierre D, Ribeiro P, Schaan B, Ribeiro J Volume of supervised exercise training impacts glycaemic control in patients with type 2 diabetes: a systematic review with meta-regression analysis.
Diabetologia 56 2 — Venables MC, Shaw CS, Jeukendrup AE, Wagenmakers AJ Effect of acute exercise on glucose tolerance following post-exercise feeding. Vollestad NK, Blom PC Effect of varying exercise intensity on glycogen depletion in human muscle fibres.
Wadden TA, Vogt RA, Foster GD, Anderson DA Exercise and the maintenance of weight loss: 1-year follow-up of a controlled clinical trial. J Consult Clin Psychol 66 2 Wadley G, Lee-Young RS, Canny BJ, Wasuntarawat C, Chen Z-P, Hargreaves M, Kemp BE, McConell GK Effect of exercise intensity and hypoxia on skeletal muscle AMPK signaling and substrate metabolism in humans.
Wahren J, Felig P, Ahlborg G, Jorfeldt L Glucose metabolism during leg exercise in man. J Clin Investig 50 12 Wallberghenriksson H, Constable SH, Young DA, Holloszy JO Glucose-transport into rat skeletal-muscle—interaction between exercise and insulin.
J Appl Physiol 65 2 — Wardzala LJ, Jeanrenaud B Potential mechanism of insulin action on glucose transport in the isolated rat diaphragm. Apparent translocation of intracellular transport units to the plasma membrane.
J Biol Chem 14 — Wasserman DH Four grams of glucose. Am J Physiol Endocrinol Metab 1 :E Wasserman DH, Spalding JA, Lacy DB, Colburn CA, Goldstein RE, Cherrington AD Glucagon is a primary controller of hepatic glycogenolysis and gluconeogenesis during muscular work.
Am J Physiol 1 Pt 1 :E Wasserman DH, Williams PE, Lacy DB, Bracy D, Cherrington AD Hepatic nerves are not essential to the increase in hepatic glucose production during muscular work. Am J Physiol 2 Pt 1 :E Metabolism 59 10 — Wiesner S, Haufe S, Engeli S, Mutschler H, Haas U, Luft FC, Jordan J Influences of normobaric hypoxia training on physical fitness and metabolic risk markers in overweight to obese subjects.
Obesity 18 1 — Winder WW, Hickson RC, Hagberg JM, Ehsani AA, McLane J Training-induced changes in hormonal and metabolic responses to submaximal exercise. J Appl Physiol 46 4 — EBioMedicine Woods D, Davison A, Stacey M, Smith C, Hooper T, Neely D, Turner S, Peaston R, Mellor A The cortisol response to hypobaric hypoxia at rest and post-exercise.
Horm Metab Res 44 04 — Würtz P, Mäkinen VP, Soininen P, Kangas AJ, Tukiainen T, Kettunen J, Savolainen MJ, Tammelin T, Viikari JS, Rönnemaa T, Kähönen M, Lehtimäki T, Ripatti S, Raitakari OT, Järvelin MR, Ala-Korpela M Metabolic signatures of insulin resistance in young adults.
Diabetes 61 6 — Young JC, Garthwaite SM, Bryan JE, Cartier LJ, Holloszy JO Carbohydrate feeding speeds reversal of enhanced glucose uptake in muscle after exercise.
Am J Physiol 5 Pt 1 :R Zinker BA, Lacy DB, Bracy D, Jacobs J, Wasserman DH a Regulation of glucose uptake and metabolism by working muscle: an in vivo analysis. Diabetes 42 7 — Zinker BA, Lacy DB, Bracy DP, Wasserman DH b Role of glucose and insulin loads to the exercising limb in increasing glucose uptake and metabolism.
J Appl Physiol — Download references. Australian National Phenome Centre, Health Futures Institute, Murdoch University, Perth, Australia.
Discipline of Exercise Science, Murdoch University, Perth, WA, , Australia. Soo, A. Raman, P. The Centre for Healthy Aging, Health Futures Institute, Murdoch University, Perth, Australia. Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve, Belgium. School of Human Sciences Exercise and Sport Science , The University of Western Australia, Crawley, WA, Australia.
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Exercise-stimulated glucose uptake — regulation and implications for glycaemic control Article 14 October Exercise-Regulated Skeletal Muscle Glucose Uptake Chapter © The Impact of Type 1 Diabetes on the Physiological Responses to Exercise Chapter © Use our pre-submission checklist Avoid common mistakes on your manuscript.
Introduction Maintaining blood glucose concentration within a narrow range is not trivial, with postprandial glycaemic excursions overlaying the fasting blood glucose concentrations.
Glucose transport Cellular uptake of glucose occurs through facilitated diffusion using a carrier protein from the glucose transporter GLUT family. Full size image. Insulin sensitivity and responsiveness Insulin sensitivity refers to the concentration of insulin required to achieve half of its maximal effect on glucose transport Holloszy Table 1 The acute and chronic hormonal responses during exercise with and without hypoxia Full size table.
Glucose transport measurement in humans The in vivo measurement of glucose transport in humans is challenging and relies on tracer-labelled glucose such as [ 13 C]glucose, [ 2 H]glucose Zinker et al.
The role of exercise intensity on glucose regulation Increasing exercise intensity results in greater recruitment of muscle fibres as well as an increased reliance on plasma glucose and muscle glycogen Coggan ; Jeukendrup ; Sahlin ; Vollestad and Blom for energy.
Changes in systemic plasma glucose post-exercise: a balance between the rate of glucose appearance and disappearance While acute exercise may increase the uptake of glucose, it should be noted that systemic plasma glucose concentration ultimately reflects the balance between the rate of glucose appearance R a or entry, and the rate of glucose disappearance R d or exit from the circulation.
Glucoregulatory effects of key hormones associated with exercise: epinephrine, glucagon, growth hormone and cortisol Increased hepatic glucose output is essential to sustaining prolonged exercise capacity and preventing hypoglycaemia Trefts et al.
Mediator to simulate or enhance the effects of exercise on glucose regulation While duration total training duration; acute session duration and intensity are important considerations, findings from longer-term training studies 6 months suggest that total work or energy expenditure is likely more important than either intensity or duration alone Houmard et al.
Stimulation of glucose uptake by hypoxia Although insulin and muscle contraction are the primary means to facilitate GLUT-4 translocation and increase glucose uptake, additional physiological stimuli including hypoxia can also increase glucose uptake Fig.
Hypoxia exposure under resting conditions on glucose tolerance and insulin sensitivity Although in vitro experiments have shown that hypoxia stimulates glucose transport via activation of GLUT-4 translocation in the myocytes, it remains unclear if similar mechanistic pathways regulating glucose uptake and GLUT-4 translocation will be activated in vivo by hypoxia in humans.
Insulin and glucose response following acute exercise bout in hypoxia Exercising in hypoxia compared to normoxia reduces oxygen availability and therefore induces a proportional shift in metabolic pathway flux Davison et al.
Effects of exercise training in hypoxia on insulin sensitivity Findings from studies assessing the effects of exercise training in hypoxia on insulin sensitivity have been inconsistent Haufe et al.
Hypoxic training—an integrated physiology approach The hypothesis that hypoxic training may potentiate the effect of exercise on glucose tolerance is based on the findings that hypoxia activates glucose transport via pathways similar to muscle contraction Kang et al.
Conclusion Systemic glucose regulation is intricately linked to cellular glucose transport, which is mediated by the translocation of glucose transport i. Data availability The data generated in the current study are available from the corresponding author on reasonable request.
Change history 27 February Missing Open Access funding information has been added in the Funding Note. References Azevedo JL, Carey JO, Pories WJ, Morris PG, Dohm GL Hypoxia stimulates glucose transport in insulin-resistant human skeletal muscle.
Diabetes 44 6 — Article CAS PubMed Google Scholar Babraj J, Vollaard N, Keast C, Guppy F, Cottrell G, Timmons J Extremely short duration high intensity interval training substantially improves insulin action in young healthy males.
BMC Endocr Disord 9 1 :3 Article PubMed PubMed Central Google Scholar Bailey DP, Smith LR, Chrismas BC, Taylor L, Stensel DJ, Deighton K, Douglas JA, Kerr CJ Appetite and gut hormone responses to moderate-intensity continuous exercise versus high-intensity interval exercise, in normoxic and hypoxic conditions.
Appetite — Article PubMed Google Scholar Bassuk SS, Manson JE Epidemiological evidence for the role of physical activity in reducing risk of type 2 diabetes and cardiovascular disease.
J Appl Physiol 99 3 — Article PubMed Google Scholar Belhaj MR, Lawler NG, Hoffman NJ Metabolomics and lipidomics: expanding the molecular landscape of exercise biology. Metabolites 11 3 Article CAS PubMed PubMed Central Google Scholar Bertoldo A, Price J, Mathis C, Mason S, Holt D, Kelley C, Cobelli C, Kelley DE Quantitative assessment of glucose transport in human skeletal muscle: dynamic positron emission tomography imaging of [ O -methylC]3- O -methyl- d -glucose.
Acta Physiol Scand 3 — Article CAS PubMed Google Scholar Boden G, Chen X, Ruiz J, White JV, Rossetti L Mechanisms of fatty acid-induced inhibition of glucose uptake.
J Clin Investig 93 6 — Article CAS PubMed PubMed Central Google Scholar Bogardus C, Thuillez P, Ravussin E, Vasquez B, Narimiga M, Azhar S Effect of muscle glycogen depletion on in vivo insulin action in man. Can J Appl Physiol 23 6 — Article CAS PubMed Google Scholar Bouissou P, Peronnet F, Brisson G, Helie R, Ledoux M Metabolic and endocrine responses to graded exercise under acute hypoxia.
Eur J Appl Physiol 55 3 — Article CAS Google Scholar Boulé N, Kenny G, Haddad E, Wells G, Sigal R Meta-analysis of the effect of structured exercise training on cardiorespiratory fitness in type 2 diabetes mellitus. Diabetologia 46 8 — Article PubMed Google Scholar Boulé NG, Weisnagel SJ, Lakka TA, Tremblay A, Bergman RN, Rankinen T, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C Effects of exercise training on glucose homeostasis: the HERITAGE Family Study.
J Appl Physiol 91 2 — Article CAS PubMed Google Scholar Brestoff JRBJ, Clippinger BCB, Spinella TST, Duvillard SPVDSV, Nindl BNB, Arciero PJAP An acute bout of endurance exercise but not sprint interval exercise enhances insulin sensitivity.
Appl Physiol Nutr Metab 34 1 —32 Article CAS PubMed Google Scholar Bruce CR, Dyck DJ Cytokine regulation of skeletal muscle fatty acid metabolism: effect of interleukin-6 and tumor necrosis factor-α. Am J Physiol-Endocrinol Metab 4 :E—E Article CAS PubMed Google Scholar Burgomaster KA, Cermak NM, Phillips SM, Benton CR, Bonen A, Gibala MJ Divergent response of metabolite transport proteins in human skeletal muscle after sprint interval training and detraining.
Am J Physiol Regul Integr Comp Physiol 5 :R—R Article CAS PubMed Google Scholar Callahan MJ, Parr EB, Hawley JA, Camera DM Can high-intensity interval training promote skeletal muscle anabolism?
Am J Physiol Endocrinol Metab E—E Article CAS Google Scholar Cartee GD, Douen AG, Ramlal T, Klip A, Holloszy J Stimulation of glucose transport in skeletal muscle by hypoxia.
J Appl Physiol 70 4 — Article CAS PubMed Google Scholar Chacaroun S, Borowik A, Gonzalez V-EY, Doutreleau S, Wuyam B, Belaidi E, Tamisier R, Pepin J-L, Flore P, Verges S Hypoxic exercise training to improve exercise capacity in obese individuals.
Med Sci Sports Exerc — Article CAS PubMed Google Scholar Chen Z-Z, Liu J, Morningstar J, Heckman-Stoddard BM, Lee CG, Dagogo-Jack S, Ferguson JF, Hamman RF, Knowler WC, Mather KJ Metabolite profiles of incident diabetes and heterogeneity of treatment effect in the diabetes prevention program.
Diabetes 68 12 — Article CAS PubMed PubMed Central Google Scholar Coderre L, Kandror KV, Vallega G, Pilch PF Identification and characterization of an exercise-sensitive pool of glucose transporters in skeletal muscle.
J Biol Chem 46 — Article CAS PubMed Google Scholar Coggan AR Plasma glucose metabolism during exercise in humans. Sports Med 11 2 — Article CAS PubMed Google Scholar Coker RH, Lacy DB, Williams PE, Wasserman DH Hepatic alpha- and beta-adrenergic receptors are not essential for the increase in R a during exercise in diabetes.
E Article CAS PubMed Google Scholar Constable SH, Favier RJ, Cartee GD, Young D, Holloszy J Muscle glucose transport: interactions of in vitro contractions, insulin, and exercise.
J Appl Physiol 64 6 — Article CAS PubMed Google Scholar Cooper D, Wasserman DH, Vranic M, Wasserman K Glucose turnover in response to exercise during high-and low-FIO2 breathing in man.
Am J Physiol Endocrinol Metab 2 :E—E Article CAS Google Scholar Craig BW, Lucas J, Pohlman R, Stelling H The effects of running, weightlifting and a combination of both on growth hormone release. J Strength Cond Res 5 4 Google Scholar Davison G, Vinaixa M, McGovern R, Beltran A, Novials A, Correig X, McClean C Metabolomic response to acute hypoxic exercise and recovery in adult males.
Diabetes Metab Syndr Obes Targets Ther Article Google Scholar De Groote E, Britto FA, Bullock L, François M, De Buck C, Nielens H, Deldicque L Hypoxic training improves normoxic glucose tolerance in adolescents with obesity.
Med Sci Sports Exerc 50 11 — Article PubMed Google Scholar De Groote E, Britto FA, Balan E, Warnier G, Thissen J-P, Nielens H, Sylow L, Deldicque L Effect of hypoxic exercise on glucose tolerance in healthy and prediabetic adults.
Am J Physiol Endocrinol Metab 1 :E43—E54 Article PubMed Google Scholar DeFronzo R, Jacot E, Jequier E, Maeder E, Wahren J, Felber J The effect of insulin on the disposal of intravenous glucose: results from indirect calorimetry and hepatic and femoral venous catheterization.
Diabetes 30 12 — Article CAS PubMed Google Scholar Dekker MJ, Graham TE, Ooi TC, Robinson LE Exercise prior to fat ingestion lowers fasting and postprandial VLDL and decreases adipose tissue IL-6 and GIP receptor mRNA in hypertriacylglycerolemic men.
E Article CAS PubMed Google Scholar Derave W, Hansen BF, Lund S, Kristiansen S, Richter EA Muscle glycogen content affects insulin-stimulated glucose transport and protein kinase B activity.
Eur J Appl Physiol 6 — Article CAS PubMed Google Scholar Dongiovanni P, Valenti L, Ludovica Fracanzani A, Gatti S, Cairo G, Fargion S Iron depletion by deferoxamine up-regulates glucose uptake and insulin signaling in hepatoma cells and in rat liver.
J Biol Chem 23 — Article CAS PubMed Google Scholar Dunn WB, Broadhurst DI, Atherton HJ, Goodacre R, Griffin JL Systems level studies of mammalian metabolomes: the roles of mass spectrometry and nuclear magnetic resonance spectroscopy. Eur J Appl Physiol 68 4 — Article CAS Google Scholar Fernández Menéndez A, Saudan G, Sperisen L, Hans D, Saubade M, Millet GP, Malatesta D Effects of short-term normobaric hypoxic walking training on energetics and mechanics of gait in adults with obesity.
J Clin Investig 72 5 Article CAS PubMed PubMed Central Google Scholar Fournier P, Bräu L, Ferreira L-B, Fairchild T, Raja G, James A, Palmer T Glycogen resynthesis in the absence of food ingestion during recovery from moderate or high intensity physical activity: novel insights from rat and human studies.
Comp Biochem Physiol a: Mol Integr Physiol 3 — Article CAS PubMed Google Scholar Fournier PA, Fairchild TJ, Ferreira LD, Bräu L Post-exercise muscle glycogen repletion in the extreme: effect of food absence and active recovery.
J Sports Sci Med 3 3 PubMed PubMed Central Google Scholar Fritsche A, Wagner R, Heni M, Kantartzis K, Machann J, Schick F, Lehmann R, Peter A, Dannecker C, Fritsche L Different effects of lifestyle intervention in high-and low-risk prediabetes: results of the randomized controlled prediabetes lifestyle intervention study PLIS.
Diabetes 70 12 — Article CAS PubMed Google Scholar Galbo H, Holst JJ, Christensen NJ Glucagon and plasma catecholamine responses to graded and prolonged exercise in man. J Clin Investig 87 3 Article CAS PubMed PubMed Central Google Scholar Gayda M, Brun C, Juneau M, Levesque S, Nigam A Long-term cardiac rehabilitation and exercise training programs improve metabolic parameters in metabolic syndrome patients with and without coronary heart disease.
Nutr Metab Cardiovasc Dis 18 2 — Article CAS PubMed Google Scholar Gillen JB, Little JP, Punthakee Z, Tarnopolsky MA, Riddell MC, Gibala MJ Acute high-intensity interval exercise reduces the postprandial glucose response and prevalence of hyperglycaemia in patients with type 2 diabetes.
Diabetes Obes Metab — Article CAS PubMed Google Scholar Girard O, Malatesta D, Millet GP Walking in hypoxia: an efficient treatment to lessen mechanical constraints and improve health in obese individuals? E Article CAS PubMed Google Scholar Güemes A, Georgiou P Review of the role of the nervous system in glucose homoeostasis and future perspectives towards the management of diabetes.
Am J Physiol Endocrinol Metab 5 :E—E Article CAS Google Scholar Gyntelberg F, Rennie M, Hickson R, Holloszy J Effect of training on the response of plasma glucagon to exercise.
J Appl Physiol 43 2 — Article CAS PubMed Google Scholar Han X-X, Bonen A Epinephrine translocates GLUT-4 but inhibits insulin-stimulated glucose transport in rat muscle.
Am J Physiol Endocrinol Metab 4 :E—E Article CAS Google Scholar Hansen PA, Nolte LA, Chen MM, Holloszy JO Increased GLUT-4 translocation mediates enhanced insulin sensitivity of muscle glucose transport after exercise.
J Appl Physiol 85 4 — Article CAS PubMed Google Scholar Hartley LH, Mason J, Hogan R, Jones L, Kotchen T, Mougey E, Wherry F, Pennington L, Ricketts P a Multiple hormonal responses to graded exercise in relation to physical training. J Appl Physiol 33 5 — Article CAS PubMed Google Scholar Hartley LH, Mason J, Hogan R, Jones L, Kotchen T, Mougey E, Wherry F, Pennington L, Ricketts P b Multiple hormonal responses to prolonged exercise in relation to physical training.
J Appl Physiol 33 5 — Article CAS PubMed Google Scholar Haufe S, Wiesner S, Engeli S, Luft FC, Jordan J Influences of normobaric hypoxia training on metabolic risk markers in human subjects.
Med Sci Sports Exerc 45 10 Article CAS PubMed PubMed Central Google Scholar Helge JW, Stallknecht B, Pedersen BK, Galbo H, Kiens B, Richter EA The effect of graded exercise on IL-6 release and glucose uptake in human skeletal muscle.
J Physiol 1 — Article CAS PubMed Google Scholar Henriksen EJ, Bourey RE, Rodnick KJ, Koranyi L, Permutt MA, Holloszy JO Glucose transporter protein-content and glucose-transport capacity in rat skeletal-muscles.
Am J Physiol 4 :E—E CAS PubMed Google Scholar Hermansen L, Vaage O Lactate disappearance and glycogen synthesis in human muscle after maximal exercise. E Article CAS PubMed Google Scholar Hill E, Zack E, Battaglini C, Viru M, Viru A, Hackney A Exercise and circulating cortisol levels: the intensity threshold effect.
J Endocrinol Invest 31 7 — Article CAS PubMed Google Scholar Hilsted J, Galbo H, Sonne B, Schwartz T, Fahrenkrug J, de Muckadell O, Lauritsen K, Tronier B Gastroenteropancreatic hormonal changes during exercise. Am J Physiol Gastrointest Liver Physiol 3 :G—G Article CAS Google Scholar Hirsch I, Marker JC, Smith LJ, Spina RJ, Parvin C, Holloszy J, Cryer P Insulin and glucagon in prevention of hypoglycemia during exercise in humans.
Am J Physiol Endocrinol Metab 5 :E—E Article CAS Google Scholar Hirshman MF, Goodyear LJ, Wardzala LJ, Horton ED, Horton ES Identification of an intracellular pool of glucose transporters from basal and insulin-stimulated rat skeletal muscle. J Biol Chem 2 — Article CAS PubMed Google Scholar Holloszy JO Exercise-induced increase in muscle insulin sensitivity.
J Appl Physiol 99 1 — Article CAS PubMed Google Scholar Holloszy J, Hansen P Regulation of glucose transport into skeletal muscle. Springer, pp 99— Google Scholar Holloszy JO, Narahara H Studies of tissue permeability X. J Biol Chem 9 — Article CAS PubMed Google Scholar Hosogai N, Fukuhara A, Oshima K, Miyata Y, Tanaka S, Segawa K, Furukawa S, Tochino Y, Komuro R, Matsuda M, Shimomura I Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation.
J Appl Physiol 96 1 — Article CAS PubMed Google Scholar Huang S, Czech MP The GLUT4 glucose transporter. Cell Metab 5 4 — Article CAS PubMed Google Scholar Hunt DG, Ivy JL Epinephrine inhibits insulin-stimulated muscle glucose transport.
J Appl Physiol 93 5 — Article CAS PubMed Google Scholar Hussey S, McGee S, Garnham A, Wentworth J, Jeukendrup A, Hargreaves M Exercise training increases adipose tissue GLUT4 expression in patients with type 2 diabetes.
Diabetes Obes Metab 13 10 — Article CAS PubMed Google Scholar Ismail N, Becker B, Strzelczyk P, Ritz E Renal disease and hypertension in non—insulin-dependent diabetes mellitus. Kidney Int 55 1 :1—28 Article CAS PubMed Google Scholar Ivy JL, Frishberg BA, Farrell SW, Miller WJ, Sherman WM Effects of elevated and exercise-reduced muscle glycogen levels on insulin sensitivity.
Am J Physiol Endocrinol Metab 1 :E—E Article CAS PubMed Google Scholar Jeukendrup AE Nutrition for endurance sports: marathon, triathlon, and road cycling.
Diabetes Care 19 4 — Article CAS PubMed Google Scholar Katz A, Broberg S, Sahlin K, Wahren J Leg glucose uptake during maximal dynamic exercise in humans. Am J Physiol Endocrinol Metab 1 :E65—E70 Article CAS Google Scholar Kawanaka K, Han DH, Nolte LA, Hansen PA, Nakatani A, Holloszy JO Decreased insulin-stimulated GLUT-4 translocation in glycogen-supercompensated muscles of exercised rats.
E Article CAS PubMed Google Scholar Kawanaka K, Nolte LA, Han DH, Hansen PA, Holloszy JO Mechanisms underlying impaired GLUT-4 translocation in glycogen-supercompensated muscles of exercised rats.
Am J Physiol Endocrinol Metab 6 :E—E Article CAS PubMed PubMed Central Google Scholar Kelly KR, Williamson DL, Fealy CE, Kriz DA, Krishnan RK, Huang H, Ahn J, Loomis JL, Kirwan JP Acute altitude-induced hypoxia suppresses plasma glucose and leptin in healthy humans.
Metabolism 59 2 — Article CAS PubMed Google Scholar Kierans SJ, Taylor CT Regulation of glycolysis by the hypoxia-inducible factor HIF : implications for cellular physiology.
J Endocrinol 1 —33 Article CAS PubMed Google Scholar Kindermann W, Schnabel A, Schmitt WM, Biro G, Cassens J, Weber F Catecholamines, growth hormone, cortisol, insulin, and sex hormones in anaerobic and aerobic exercise.
J Appl Physiol 78 1 —22 Article CAS PubMed Google Scholar Kjaer M Hepatic glucose production during exercise. Adv Exp Med Biol — Article CAS PubMed Google Scholar Kjaer M, Bangsbo J, Lortie G, Galbo H Hormonal response to exercise in humans: influence of hypoxia and physical training.
Am J Physiol Regul Integr Comp Physiol 2 :R—R Article CAS Google Scholar Kjaer M, Hollenbeck C, Frey-Hewitt B, Galbo H, Haskell W, Reaven G Glucoregulation and hormonal responses to maximal exercise in non-insulin-dependent diabetes.
J Appl Physiol 68 5 — Article CAS PubMed Google Scholar Klug L, Mähler A, Rakova N, Mai K, Schulz-Menger J, Rahn G, Busjahn A, Jordan J, Boschmann M, Luft FC Normobaric hypoxic conditioning in men with metabolic syndrome.
Physiol Rep 6 24 :e Article PubMed PubMed Central Google Scholar Knudsen SH, Karstoft K, Pedersen BK, van Hall G, Solomon TP The immediate effects of a single bout of aerobic exercise on oral glucose tolerance across the glucose tolerance continuum.
Physiol Rep 2 8 :e Article PubMed PubMed Central Google Scholar Kon M, Nakagaki K, Ebi Y, Nishiyama T, Russell AP Hormonal and metabolic responses to repeated cycling sprints under different hypoxic conditions. J Appl Physiol 3 — Article CAS PubMed Google Scholar Krug S, Kastenmüller G, Stückler F, Rist MJ, Skurk T, Sailer M, Raffler J, Römisch-Margl W, Adamski J, Prehn C The dynamic range of the human metabolome revealed by challenges.
FASEB J 26 6 — Article CAS PubMed Google Scholar Kullman EL, Kelly KR, Haus JM, Fealy CE, Scelsi AR, Pagadala MR, Flask CA, McCullough AJ, Kirwan JP Short-term aerobic exercise training improves gut peptide regulation in nonalcoholic fatty liver disease.
J Physiol 1 — Article CAS PubMed PubMed Central Google Scholar Laukkanen JA, Mäkikallio TH, Ronkainen K, Karppi J, Kurl S Impaired fasting plasma glucose and type 2 diabetes are related to the risk of out-of-hospital sudden cardiac death and all-cause mortality.
Diabetes Care 36 5 — Article CAS PubMed PubMed Central Google Scholar Lawler NG, Abbiss CR, Gummer JPA, Broadhurst DI, Govus AD, Fairchild TJ, Thompson KG, Garvican-Lewis LA, Gore CJ, Maker GL, Trengove RD, Peiffer JJ Characterizing the plasma metabolome during 14 days of live-high, train-low simulated altitude: a metabolomic approach.
J Appl Physiol 6 — Article CAS PubMed Google Scholar Luger A, Deuster PA, Kyle SB, Gallucci WT, Montgomery LC, Gold PW, Loriaux DL, Chrousos GP Acute hypothalamic—pituitary—adrenal responses to the stress of treadmill exercise.
N Engl J Med 21 — Article CAS PubMed Google Scholar Lund S, Holman G, Schmitz O, Pedersen O Contraction stimulates translocation of glucose transporter GLUT4 in skeletal muscle through a mechanism distinct from that of insulin.
Proc Natl Acad Sci 92 13 — Article CAS PubMed PubMed Central Google Scholar Lundby C, Van Hall G Substrate utilization in sea level residents during exercise in acute hypoxia and after 4 weeks of acclimatization to m.
Acta Physiol Scand 3 — Article CAS PubMed Google Scholar MacInnis MJ, Gibala MJ Physiological adaptations to interval training and the role of exercise intensity. Diabetes Metab Res Rev 27 1 — Article PubMed Google Scholar Mackenzie R, Elliott B, Maxwell N, Brickley G, Watt P a The effect of hypoxia and work intensity on insulin resistance in type 2 diabetes.
J Clin Endocrinol Metab 97 1 — Article CAS PubMed Google Scholar Mackenzie R, Maxwell N, Castle P, Elliott B, Brickley G, Watt P b Intermittent exercise with and without hypoxia improves insulin sensitivity in individuals with type 2 diabetes. J Clin Endocrinol Metab 97 4 :E—E Article CAS PubMed Google Scholar MacLeod S, Terada T, Chahal B, Boulé N Exercise lowers postprandial glucose but not fasting glucose in type 2 diabetes: a meta-analysis of studies using continuous glucose monitoring.
Diabetes Metab Res Rev 29 8 — Article CAS PubMed Google Scholar Marliss EB, Simantirakis E, Miles P, Purdon C, Gougeon R, Field CJ, Halter JB, Vranic M Glucoregulatory and hormonal responses to repeated bouts of intense exercise in normal male subjects.
J Appl Physiol 71 3 — Article CAS PubMed Google Scholar Matu J, Deighton K, Ispoglou T, Duckworth L The effect of moderate versus severe simulated altitude on appetite, gut hormones, energy intake and substrate oxidation in men. Acta Physiol 1 — Article CAS Google Scholar Medzhitov R Origin and physiological roles of inflammation.
Nature — Article CAS PubMed Google Scholar Mendenhall LA, Swanson SC, Habash DL, Coggan AR Ten days of exercise training reduces glucose production and utilization during moderate-intensity exercise.
Am J Physiol Endocrinol Metab 1 :E—E Article CAS Google Scholar Mendes R, Sousa N, Almeida A, Subtil P, Guedes-Marques F, Reis VM, Themudo-Barata JL Exercise prescription for patients with type 2 diabetes—a synthesis of international recommendations: narrative review.
Br J Sports Med 50 22 — Article PubMed Google Scholar Mikines KJ, Sonne B, Farrell P, Tronier B, Galbo H Effect of physical exercise on sensitivity and responsiveness to insulin in humans.
Am J Physiol Endocrinol Metab 3 :E—E Article CAS Google Scholar Mikus CR, Oberlin DJ, Libla JL, Taylor AM, Booth FW, Thyfault JP Lowering physical activity impairs glycemic control in healthy volunteers.
Rapid reversal of adaptive increases in muscle GLUT-4 and glucose transport capacity after training cessation. This effect may remain for up to 48 hours after physical activity, suggesting the need of practice in a chronic manner to obtain its benefits continuously.
The identification of GLUT-4, abundantly expressed in adipose and muscle tissue, favored further studies about the mechanisms by which exercise can influence glucose uptake by skeletal muscle tissue 9 9 Charron MJ, Brosius FC, Alper SL, Lodish HF.
A glucose transport protein expressed predominately in insulin-responsive tissues. Proc Natl Acad Sci U S A. Studies in animal models 10 10 Luciano E, Carneiro EM, Carvalho CRO, Carvalheira JBC, Peres SB, Reis MAB, et al.
Eur J Endocrinol. Effects of Physical Exercise in the Ampkα Expression and Activity in High-fat Diet Induced Obese Rats. Rev Bras Med do Esporte. as well asin humans 12 12 Christ-Roberts CY, Pratipanawatr T, Pratipanawatr W, Berria R, Belfort R, Kashyap S, et al.
Exercise training increases glycogen synthase activity and GLUT4 expression but not insulin signaling in overweight nondiabetic and type 2 diabetic subjects. Exercise training increases insulin-stimulated glucose disposal and GLUT4 SLC2A4 protein content in patients with type 2 diabetes.
Effects of endurance exercise training on insulin signaling in human skeletal muscle: interactions at the level of phosphatidylinositol 3-kinase, Akt, and AS have shown that physical training increases the expression of GLUT-4, promoting glucose uptake in skeletal muscle. Although the identification of the GLUT-4 has been very important, the following findings allowed to understand that exercise exerts actions on other molecules involved in glucose uptake.
Glucose uptake utilizes insulin-dependent and insulin-independent cell signalingpathways. The finding and understanding about the mechanisms of action of some proteins that act independently of insulin on glucose uptake allow to definitely recognize the benefits of using exercise as a non-pharmacological tool in the control of glucose homeostasis and in preventing and treating diabetes.
Therefore, this mini-review aims to describe the different mechanisms involved in glucose uptake at rest and in response to physical exercise.
Glucose uptake by insulin stimulation occurs after the hormone binds to its specific membrane receptor called insulin receptor IR 16 16 Leney SE, Tavaré JM. The molecular basis of insulin-stimulated glucose uptake: signalling, trafficking and potential drug targets.
J Endocrinol. The IR is a heterotetrameric protein with intrinsic tyrosine kinase activity. After this binding, the receptor undergoes a conformational alteration, triggering its autophosphorylation on tyrosine residues. Once activated, IR promotes the tyrosine phosphorylation of different substrates, including insulin receptor substrates 1 and 2 IRS-1 and IRS The tyrosine phosphorylation of IRS-1 and IRS-2 allows them to associate and activate the phosphatidylinositol-3 kinase enzyme PI3K.
PI3K catalyzes the phosphorylation of membrane phosphoinositides at the position3 of the inositol ring to produce phosphatidylinositol 3-phosphate, phosphatidylinositol 3,4-phosphate and phosphatidylinositol-3,4,5-phosphate.
The latter product regulates the activity of phosphoinositide-dependent kinase-1 PDK When active, the Akt is responsible for the activation of AS Akt substrate of kDa 16 16 Leney SE, Tavaré JM. The AS can act in two significant ways on GLUT4 translocation to the periphery: 1 by reducing the "tethering" of the vesicle, by proteins called TUG, and thus releasing it to the periphery; 2 byincreasing the activity of Rab proteins which will stimulate the translocation of these vesicles containing GLUT4 to the periphery.
Therefore, these activation mechanisms and the release of vesicles containing GLUT4 are essential for glucose homeostasis at baseline. The increase of GLUT4 and its translocation to the sarcoplasm are extremely important for performance and health 16 16 Leney SE, Tavaré JM.
Several studies have indicated that compromise at some point in this pathway can decrease glucose uptake, triggering important physiological changes that can lead to the development of various metabolic diseases, such as diabetes 17 17 Hotamisligil GS.
Inflammation and metabolic disorders 1. However, it is worth mentioning that there are alternative pathways in addition to insulin that are responsiblefor regulating glucose uptake, acting jointly in the regulation of glucose homeostasis. For example, studies using MIRKO animals mice without insulin receptor in skeletal muscles - muscle insulin receptor knockout show that there is reduced insulin signaling but no effect on the IGF-1 pathway insulin-like growth factor, a growth factor similar to insulin , indicating that different pathways can act in a compensatory fashion to maintain signaling 18 18 He Z, Opland DM, Way KJ, Ueki K, Bodyak N, Kang PM, et al.
Arterioscler Thromb Vasc Biol. As there is homology between the molecules in the absence of insulin, IGF receptor receives the insulin signal and propagates intracellularly, partially compensating its absence.
Thus, it is necessary to address some of the main mechanisms to promote glucose uptake, even in conditions of low levels of circulating insulin. In skeletal muscle, glucose uptake depends on the presence of GLUT-4 on the cell membrane, so that it exerts its function of allowing the entry of glucose by facilitated diffusion.
At baseline conditions, the great majority of GLUT4 molecules is stored in vesicles within the cell, keeping it in a quiescent, waiting for the recruitment signal. Therefore, under resting conditions, insulin is essential for glucose uptake in muscle tissue 19 19 Bradley H, Shaw CS, Bendtsen C, Worthington PL, Wilson OJ, Strauss JA, et al.
Visualization and quantitation of GLUT4 translocation in human skeletal muscle following glucose ingestion and exercise. Physiol Rep.
During exercise, there is an increase in blood flow to the active muscles, creating an incentive for the dilation of blood vessels responsible for irrigation of active muscles, thereby aiming to increase the surface area available for transport of glucose 20 20 Andersen P, Saltin B.
Maximal perfusion of skeletal muscle in man. J Physiol. During muscle contraction, circulating insulin levels suffer no significant change, and in some cases even suffer a decrease.
Thus, the muscle contractions and blood flow circulating levels of insulin act in synergism generating signals for translocation of GLUT4 to the membrane of the sarcolemma and t-tubules, thereby increasing glucose uptake by the cell 21 21 Richter EA, Hargreaves M. Exercise, GLUT4, and Skeletal Muscle Glucose Uptake.
Physiol Rev. The amount of GLUT4 present in the sarcolemma and in the t-tubules is influenced by the efficiency of endocytosis and exocytosis processes of vesicles containing the protein in its inactive form. Insulin increases the amount of GLUT4 in muscle membrane primarily by increasing the stimulation of exocytosis 22 22 Stöckli J, Fazakerley DJ, James DE.
GLUT4 exocytosis. J Cell Sci. The GLUT4 glucose transporter. Cell Metab. This phenomenon may explain the additive effect of exercise on insulin in muscle glucose uptake 24 24 Ploug T, Galbo H, Vinten J, Jørgensen M, Richter EA.
Kinetics of glucose transport in rat muscle: effects of insulin and contractions. Am J Physiol. The understanding that exercise cooperates in glucose uptake has led many researchers to investigate which mechanisms could be linked to muscle contraction and independently to the hormone insulin.
Increases of both glucose uptake and metabolism in response to exercise are often associated with the effects of a single session of exercise in the levels of mRNA and in the absolute levels of GLUT-4 25 25 Kraniou Y, Cameron-Smith D, Misso M, Collier G, Hargreaves M.
Effects of exercise on GLUT-4 and glycogenin gene expression in human skeletal muscle. In addition to increased levels of GLUT-4, exercise is able to increase GLUT-4 translocation to myocellular membrane related to increased exocytosis rate and lower endocytosis rate, as previously discussed , increasing the glucose uptake capacity in muscle cells 19 19 Bradley H, Shaw CS, Bendtsen C, Worthington PL, Wilson OJ, Strauss JA, et al.
The effects of exercise in increasing GLUT4 content and translocation involve some molecules that will be presented below. A few years before the description of AMPK activation by physical exercise and related experimental evidence in humans, animal researches identified a drug compound known to act as a potent activator of this molecule, AICAR 5-aminoimidazole ribonucleotidecarboxamide.
This compound, that mimics the intracellular increase in AMP, is capable of phosphorylatingAMPK promoting glucose uptake and lipid oxidation in skeletal muscle 26 26 Merrill GF, Kurth EJ, Hardie DG, Winder WW. AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle.
Animal experiments also suggest that AMPK activation in skeletal muscle is capable of enhancinglipid oxidation and the glycogen resynthesisrate in response to exercise having a protective effect on muscle glycogen stores through the muscle contraction stimulus per se and throughthe increase of calcium release 27 27 Jeon SM.
Regulation and function of AMPK in physiology and diseases. Exp Mol Med. Nature Publishing Group; ;48 7 :e Continuous and repetitive muscle contractionthat is characteristic of exercise acts as a stressor agent.
This activity causes depletion momentary or extended of ATP levels, which are rapidly resynthesized. However, at any given time, cellular ATP resynthesis becomes insufficient due to decreased levels of the enzyme creatine phosphate CP or even glucose, causing an increase in the ADP:ATP ratio and, consequently, in the AMP:ATP ratio.
This phenomenon promotes the phosphorylation of LKB1 liver kinase B1 - B1 liver kinase which phosphorylates and activates AMPK, which can finally phosphorylate the AS protein 28 28 Stanford KI, Goodyear LJ. Exercise and type 2 diabetes: molecular mechanisms regulating glucose uptake in skeletal muscle.
Adv Physiol Educ. AMPK-mediated AS phosphorylation in skeletal muscle is dependent on AMPK catalytic and regulatory subunits. The AS can act in various ways to translate GLUT4-containing vesicles to the periphery. One is through the activation of Rab-GTP protein, which will trigger signal for the translocation of GLUT4 30 30 Cartee GD.
Mechanisms for greater insulin-stimulated glucose uptake in normal and insulin-resistant skeletal muscle after acute exercise. American Physiological SocietyAm J Physiol Endocrinol Metab; ; 12 :E Another way is by reducing the TUG activity, protein "tethering" which binds to the vesicles, preventing its translocation 31 31 Bogan JS, Hendon N, McKee AE, Tsao TS, Lodish HF.
Functional cloning of TUG as a regulator of GLUT4 glucose transporter trafficking. Additionally, AMPK phosphorylates HDAC5 histone deacetylase 5 , which is exported from the nucleus promoting the activation of MEF2 stimulating factor of myocyte 2 and GEF stimulating factor GLUT4 as well as their combination.
Both these transcription factors are related to the GLUT4 expression in skeletal muscle 32 32 McGee SL, Sparling D, Olson AL, Hargreaves M. Exercise increases MEF2- and GEF DNA-binding activity in human skeletal muscle.
FASEB J. Thus, in addition to causing the translocation of GLUT4 molecules to the membrane, AMPK in its active form is also capable of regulatingthe expression of new GLUT-4 molecules. Calcium ions have gained attention in recent decades due to their contribution to glucose uptake. Early studies found their participation in glucose homeostasis, when Sartorius muscle of frogs were incubated with caffeine 33 33 Holloszy JO, Narahara HT.
Enhanced permeability to sugar associated with muscle contraction. J Gen Physiol. Based on these results, it was observed that caffeine stimulates calcium release from the sarcoplasmic reticulum without plasma membrane depolarization and that this influx per se was sufficient to stimulate glucose uptake.
Subsequently, studies with rat muscles incubated with caffeine or a chemical compound, which also stimulates calcium release in sufficient levels to promote muscle contraction 34 34 Holloszy JO, Narahara HT.
Nitrate Ions: Potentiation of Increased Permeability to Sugar Associated with Muscle Contraction. Since the increase in energy expenditure is responsible for the activation of AMPK, and it triggers processes that signalfor the translocation of GLUT4 from intracellular vesicles to the plasma membrane, glucose uptake will be stimulated 15 15 Witczak CA, Fujii N, Hirshman MF, Goodyear LJ.
Calmodulin-dependent protein kinase kinase-β is an alternative upstream kinase for AMP-activated protein kinase. Due to this, some studies were developed to examine this pathway in muscle tissue of rodents, but they showed controversial results 15 15 Witczak CA, Fujii N, Hirshman MF, Goodyear LJ.
Calcium stimulates glucose transport in skeletal muscle by a pathway independent of contraction. Exercise and Regulation of Carbohydrate Metabolism. Prog Mol Biol Transl Sci. Some studies suggested the role of ROS in glucose uptake in response to muscle contraction, due to the fact that exercise increases significantly and transiently the production of ROS 38 38 Reid MB.
Free radicals and muscle fatigue: Of ROS, canaries, and the IOC. Free Radic Biol Med. AMPK alpha1 activation is required for stimulation of glucose uptake by twitch contraction, but not by H2O2, in mouse skeletal muscle. PLoS One. Some experiments that used donor ROS treatment in isolated skeletal muscle fibers observed that glucose uptake in the treated muscles was higher 39 39 Jensen TE, Schjerling P, Viollet B, Wojtaszewski JFP, Richter EA.
Other studies using non-specific inhibitors of ROS found divergent results, with no effect on glucose uptake in both rodents 40 40 Merry TL, Dywer RM, Bradley EA, Rattigan S, McConell GK. Local hindlimb antioxidant infusion does not affect muscle glucose uptake during in situ contractions in rat.
Glucose Promoting bone health in athletes is an important metaboolism for cell homeostasis Metabolisk for organism health. Under resting conditions, skeletal muscle Exercise and glucose metabolism dependent on insulin to glucpse glucose uptake. Insulin, after binding to its Exercise and glucose metabolism receptor, triggers a cascade of intracellular reactions culminating Sports Performance Workshops activation of the glucose Exerciee 4, GLUT4, among other outcomes. This transporter migrates to the plasma membrane and assists in glucose internalization. However, under special conditions such as physical exercise, alterations in the levels of intracellular molecules such as ATP and calcium actto regulate GLUT4 translocation and glucose uptake in skeletal muscle, regardless of insulinlevels. Regular physical exercise, due to stimulating pathways related to glucose uptake, is an important non-pharmacological intervention for improving glycemic control in obese and diabetic patients. In this mini-review the main mechanisms involved in glucose uptake in skeletal muscle in response to muscle contraction will be investigated.
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