Article CAS Google Scholar Stephens, F. Article PubMed PubMed Glucoes Google Scholar. Acta Physiol. Unsurprisingly, high-intensity exercise is now widely accepted and recommended for individuals with T2DM Mendes et al.

Exercise and glucose metabolism -

Knowledge of the relationship between exercise and glucose metabolism benefits athletes as well as sedentary individuals and those suffering from type 2 diabetes. When worried about which exercise is best for reaching specific athletic or therapeutic goals, seek the help of trusted professionals to make up for the knowledge deficit and lower risk of injury or self-harm.

Your email address will not be published. Jaimi's Desk. Regular exercise is one of the best ways to promote health and manage chronic illnesses. The relationship between exercise and glucose metabolism, specifically, is important for everyone to know about.

Skeletal Muscle and Athletes Skeletal muscle is one of the primary consumers of carbohydrates as glucose to generate energy in the form of ATP adenosine triphosphate to fuel movement. Non-Athletes and Blood Sugar Athletes are not the only ones who should care about the effects of exercise on glucose metabolism in skeletal muscle.

Type 2 Diabetes Exercise is known to improve insulin sensitivity. Take Home Point Exercise is an important part of health for everyone. Refe rences- Mul, J.

Neuregulins mediate calcium-induced glucose transport during muscle contraction. Roustit, M. Urocortin 3 activates AMPK and AKT pathways and enhances glucose disposal in rat skeletal muscle. MacDonald, C. Interleukin-6 release from human skeletal muscle during exercise: relation to AMPK activity. Article Google Scholar.

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Diabetes 55 , — IL-6 is not essential for exercise-induced increases in glucose uptake. Benrick, A. Interleukin-6 mediates exercise-induced increase in insulin sensitivity in mice. Buvinic, S. ATP released by electrical stimuli elicits calcium transients and gene expression in skeletal muscle.

Taguchi, T. Compression-induced ATP release from rat skeletal muscle with and without lengthening contraction. Mortensen, S. Muscle interstitial ATP and norepinephrine concentrations in the human leg during exercise and ATP infusion.

Casas, M. ATP signaling in skeletal muscle: from fiber plasticity to regulation of metabolism. Sport Sci. Akt and Rac1 signaling are jointly required for insulin-stimulated glucose uptake in skeletal muscle and downregulated in insulin resistance.

Lee, A. Wortmannin inhibits insulin-stimulated but not contraction-stimulated glucose transport activity in skeletal muscle. FEBS Lett. Kinetics of glucose transport in rat muscle: effects of insulin and contractions. Lund, S. Contraction stimulates translocation of glucose transporter GLUT4 in skeletal muscle through a mechanism distinct from that of insulin.

USA 92 , — Acute exercise and physiological insulin induce distinct phosphorylation signatures on TBC1D1 and TBC1D4 proteins in human skeletal muscle. Rac1 in muscle is dispensable for improved insulin action after exercise in mice.

Endocrinology , — Kjobsted, R. Prior AICAR stimulation increases insulin sensitivity in mouse skeletal muscle in an AMPK-dependent manner. Enhanced leg glucose uptake and normal hepatic glucose output during exercise in patients with NIDDM [abstract]. Diabetes 42 Suppl.

Wallberg-Henriksson, H. Activation of glucose transport in diabetic muscle: responses to contraction and insulin.

DeFronzo, R. Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care 32 Suppl. Effect of training on the dose-response relationship for insulin action in men.

Calphostin C is an inhibitor of contraction, but not insulin-stimulated glucose transport, in skeletal muscle. Possible CaMKK-dependent regulation of AMPK phosphorylation and glucose uptake at the onset of mild tetanic skeletal muscle contraction. Koh, H. Sucrose nonfermenting AMPK-related kinase SNARK mediates contraction-stimulated glucose transport in mouse skeletal muscle.

Deficiency of LKB1 in skeletal muscle prevents AMPK activation and glucose uptake during contraction. EMBO J. Jeppesen, J. LKB1 regulates lipid oxidation during exercise independently of AMPK.

Mu, J. Jr, Valladares, O. A role for AMP-activated protein kinase in contraction- and hypoxia-regulated glucose transport in skeletal muscle.

Cell 7 , — Lefort, N. The α-subunit of AMPK is essential for submaximal contraction-mediated glucose transport in skeletal muscle in vitro.

Maarbjerg, S. Genetic impairment of α2-AMPK signaling does not reduce muscle glucose uptake during treadmill exercise in mice. Skeletal muscle AMP-activated protein kinase is essential for the metabolic response to exercise in vivo.

Jorgensen, S. Fentz, J. AMPKα is critical for enhancing skeletal muscle fatty acid utilization during in vivo exercise in mice. Contraction- and hypoxia-stimulated glucose transport in skeletal muscle is affected differently by wortmannin.

Evidence for different signalling mechanisms. Acta , — Knockout of the predominant conventional PKC isoform, PKCα, in mouse skeletal muscle does not affect contraction-stimulated glucose uptake.

Calmodulin-binding domain of AS regulates contraction- but not insulin-stimulated glucose uptake in skeletal muscle. Vichaiwong, K.

Contraction regulates site-specific phosphorylation of TBC1D1 in skeletal muscle. An, D. TBC1D1 regulates insulin- and contraction-induced glucose transport in mouse skeletal muscle. Glucose kinetics and exercise tolerance in mice lacking the GLUT4 glucose transporter. Skeletal muscle glucose uptake during treadmill exercise in neuronal nitric oxide synthase-μ knockout mice.

Halseth, A. Overexpression of hexokinase II increases insulinand exercise-stimulated muscle glucose uptake in vivo. Hexokinase II partial knockout impairs exercise-stimulated glucose uptake in oxidative muscles of mice. Decreased insulin action in skeletal muscle from patients with McArdle's disease.

Download references. and M. are supported by Postdoctoral Fellowships from the Danish Council for Independent Research Medical Sciences grants — and —, respectively. is supported by an excellence grant from the Novo Nordisk Foundation grant Department of Nutrition, Molecular Physiology Group, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.

Lykke Sylow, Maximilian Kleinert, Erik A. Institute for Diabetes and Obesity, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.

You can also search for this author in PubMed Google Scholar. and T. researched the data for the article. provided a substantial contribution to discussions of the content. Correspondence to Erik A.

Reprints and permissions. Exercise-stimulated glucose uptake — regulation and implications for glycaemic control. Nat Rev Endocrinol 13 , — Download citation. Published : 14 October Issue Date : March Anyone you share the following link with will be able to read this content:.

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Skip to main content Thank you for visiting nature. nature nature reviews endocrinology review articles article. Subjects Energy metabolism Insulin signalling Metabolism Skeletal muscle Type 2 diabetes. Abstract Skeletal muscle extracts glucose from the blood to maintain demand for carbohydrates as an energy source during exercise.

Access through your institution. Buy or subscribe. Change institution. Learn more. Figure 1: Exercise enhances insulin sensitivity. Figure 2: Molecular mechanisms of exercise-regulated glucose uptake by skeletal muscle.

Figure 3: An integrated view of exercise-stimulated glucose uptake. References Wasserman, D. Article CAS PubMed Google Scholar Hoffman, N. Article CAS PubMed PubMed Central Google Scholar Jensen, T. Article CAS PubMed Google Scholar Jordy, A. Article CAS PubMed Google Scholar Jensen, T.

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Article PubMed PubMed Central CAS Google Scholar Sen, C. Article CAS PubMed Google Scholar Gomez-Cabrera, M. Article CAS PubMed PubMed Central Google Scholar Svensson, M. There are 14 facilitative glucose transporter proteins encoded in the human genome Mueckler and Thorens Of these, glucose transporter type 1 GLUT-1 is ubiquitously distributed and does not change in response to hormonal or other stimuli Douen et al.

For this reason, GLUT-1 is primarily responsible for glucose transport under basal conditions. Glucose transporter type 4 GLUT-4 , is present primarily in adipose cells Garvey et al.

Of the several glucose transporters including GLUT-1, GLUT-5 and GLUT, GLUT-4 is the predominant protein expressed in the skeletal muscle Stuart et al.

That said, the GLUT-4 protein content varies between muscle fibre types Henriksen et al. In this instance, GLUT-4 displays membrane trafficking capability Huang and Czech that is highly responsive to insulin, muscle contraction and other stimuli e. hypoxia Richter et al.

Accordingly, GLUT-4 is likely responsible for the bulk of glucose uptake into the muscle and is, therefore, an important determinant of glucose homeostasis.

Insulin plays a central role in glucose homeostasis through its direct effect on insulin-sensitive tissues, namely, the liver, adipose tissues and skeletal muscle Petersen and Shulman In this instance, an increased GLUT-4 protein content at the cell membrane ultimately increases the rate of glucose transport Constable et al.

Specifically, the increase in GLUT-4 content and glucose transport parallels the increased contraction rates Lund et al. This additive effect in skeletal muscle may be due to the existence of discrete intracellular GLUT-4 pools, which are mobilized via distinct molecular mechanisms Coderre et al.

That said, the molecular mechanisms stimulating GLUT-4 translocation during insulin stimulation and contraction do appear to partially converge at the Rab GTPase-activating protein GAP AKT substrate of kDa AS or also known as TBC1D4 and GAP TBC1D1 Mackenzie and Watt ; Sylow et al.

Rac1 Sylow et al. Upon insulin binding, the activated insulin receptor initiates downstream metabolic signalling that recruits diverse substrates, which ultimately leads to the translocation and fusion of the glucose transporter storage vesicle to the cell membrane and insertion of GLUT Exercise and muscle contraction stimulate GLUT-4 translocation and glucose uptake through a distinct mechanism independent of insulin.

Hypoxia activates GLUT-4 translocation via similar or overlapping pathways to that of contraction-mediated glucose uptake. These findings in rat epitrochlearis muscle provided early evidence that glucose uptake after exercise occurs in two phases. An additive effect of insulin and exercise on glucose uptake during the early stages of recovery; followed by an increase in insulin sensitivity and responsiveness during the latter stages of recovery when contraction-mediated glucose uptake had largely been reversed Wallberghenriksson et al.

Insulin sensitivity refers to the concentration of insulin required to achieve half of its maximal effect on glucose transport Holloszy Conversely, insulin responsiveness refers to the rate of glucose transport associated with a maximally effective insulin. In this instance, the measurement of insulin sensitivity post-exercise requires careful interpretation to distinguish between increased insulin action i.

The duration of increased insulin sensitivity following exercise may persist from 3 to 48 h and is dependent on the dietary status Cartee et al.

In rats fed a carbohydrate-free diet post-exercise, the exercise-stimulated increases in glucose uptake 7. These findings support the observations that insulin-mediated glucose uptake and GLUT4 translocation in the skeletal muscle of rats, are directly associated with muscle glycogen concentration Host et al.

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 tracer-labelled glucose is coupled with either tissue biopsies Roussel et al. Using arterio-venous glucose differences, skeletal muscle glucose transport was shown to increase with intensity as well as duration during knee extensions in humans Kjaer et al. For instance, glucose uptake rates of 0.

The greater recruitment of total muscle fibres, and in particular fast-twitch fibres, likely underpins the higher rates of glucose uptake at higher work capacities Katz et al. 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.

Furthermore, increased utilization and reduction of muscle glycogen are associated with improved glucose uptake in the skeletal muscle of rats Host et al. Hence, it is tenable to expect that high-intensity exercise enhances glucose tolerance.

Similarly, there were no differences in plasma glucose response to an oral glucose tolerance test OGTT performed 1 h and 24 h after a moderate- or high-intensity exercise bout in healthy, middle-aged individuals Bonen et al.

In contrast, in prediabetic adults the plasma glucose and insulin response to an OGTT were improved 1 h post an isocaloric moderate- or high-intensity exercise bout, although the high-intensity exercise improved insulin sensitivity to a greater degree than the moderate-intensity exercise bout Rynders et al.

HIIE results in significant muscle glycogen depletion Hermansen and Vaage , which would be expected to elicit increased skeletal muscle glucose uptake. This was due largely to reduced fasting plasma insulin concentration rather than changes in glucose concentration and insulin AUC during the OGTT Brestoff et al.

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.

Glucose R a in the fasted state is principally governed by total hepatic glucose release. Glucose R a in the postprandial period is governed by total hepatic glucose release and the glucose remaining in the portal vein dietary glucose absorbed from the small intestine following hepatic first-pass.

The R d is the sum of glucose uptake by all cells of the body. In this instance, the balance between R a and R d becomes more complex during exercise since both R a and R d are affected. Furthermore, during high-intensity exercise, a host of glucoregulatory hormones described below , rather than insulin per se, become the key regulators of glucose regulation.

Increased hepatic glucose output is essential to sustaining prolonged exercise capacity and preventing hypoglycaemia Trefts et al. This increased hepatic glucose output coincides with increases in glucagon, catecholamine and cortisol concentrations and decreases in insulin concentration Wasserman ; Kindermann et al.

Of these hormones, single infusions of epinephrine and glucagon during resting conditions are associated with increases in plasma glucose, with glucagon increasing hepatic glucose output to the greatest level, while cortisol appears to have negligible effect in isolation Eigler et al.

Glucagon, in concert with the associated decrease in insulin concentration, likely plays the greatest role in increasing hepatic glucose release during exercise Hirsch et al.

In contrast, the influences of catecholamines, and specifically epinephrine on increased hepatic glucose output, appear minimal Wasserman et al. Several hormones appear to act synergistically on hepatic glucose production, with the addition of epinephrine and glucagon being greater than either alone, and the addition of cortisol prolonging the action of these hormones on the liver Eigler et al.

Glucoregulatory effects of key hormones controlling plasma glucose concentration. Effect of insulin on the liver, adipose tissue and skeletal muscle pathways are demonstrated, along with counter-regulatory effects of epinephrine and norepinephrine, growth hormone and glucagon. While the effects of glucagon may be largely limited to the liver, epinephrine can play important roles in R d Sherwin et al.

The underlying mechanisms associated with the downregulation of insulin-stimulated glucose transport with epinephrine is likely associated with a decreased activity of insulin receptor substrate-1 associated phosphatidylinositol 3-kinase PI3K Hunt and Ivy Circulating levels of growth hormone GH are increased with exercise Hirsch et al.

The role of GH in glucose regulation is complex and appears to occur in two phases with an initial, transient, insulin-like response followed by an anti-insulin response in the hours thereafter Rizza et al. The anti-insulin effects of GH include the promotion of gluconeogenesis and hepatic glucose release Schwarz et al.

GH was shown to reduce glucose uptake in an in vivo adipocyte model Kilgour et al. Muscle glucose uptake also decreases Jessen et al.

Increases in growth hormone, as well as epinephrine, also increase lipolysis, and consequently increased FFA concentrations Schwarz et al. The increase in circulating FFA interferes with glucose uptake via both insulin-dependent Stefan et al.

Given the complex interactions of systemic glucoregulatory factors governing glucose R a and R d in response to exercise, it may come as no surprise that there are discrepancies in studies assessing postprandial glucose tolerance in response to acute exercise.

Some studies found glucose tolerance to remain unchanged Roberts et al. Whilst longer-term improvement in glycaemic control with exercise training is firmly established Umpierre et al.

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. Not surprisingly, efforts have been made to identify the potential stimulus that may bypass the defects in insulin signalling in skeletal muscle.

Alternative strategies, which may potentiate the effects of exercise at a reduced dose, have, therefore, been explored. One such strategy is exercise training in hypoxia i.

This is of particular relevance since skeletal muscle glycogen concentration is a potent regulator of insulin sensitivity and therefore, systemic glucose homeostasis Shearer and Graham Furthermore, hypoxia may also stimulate the activation of signalling molecules De Groote and Deldicque , increasing glucose uptake similar to high-intensity exercise.

As such, hypoxic exercise may represent an alternate strategy to enhance glycaemic control via enhanced glucose metabolism. Accordingly, the following sections attempt to synthesize the effects of systemic hypoxia, with and without exercise on glucose homeostasis. 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.

For example, Cartee et al. These findings indicate that hypoxia stimulates glucose uptake via similar mechanisms to contraction-simulated pathways. Additionally, hypoxia-inducible factors HIFs are activated upon cellular exposure to hypoxia Semenza , HIF1ɑ has been implicated in the regulation of AKT activity in human HepG2 cells Dongiovanni et al.

These findings showing that hypoxia similar to exercise may stimulate glucose transport via pathways distinct from insulin imply that hypoxia may be a relevant strategy to improve glucose tolerance in individuals with insulin resistance.

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.

In one of the first studies to examine the effects of acute hypoxia for 4 h on intramuscular insulin signalling following a high glycaemic meal in healthy humans, D'Hulst et al. Together, this result suggested that hypoxia may reduce glucose response to a high glycaemic meal by increasing the abundance of GLUT-4 at the sarcolemmal through insulin-independent pathways D'Hulst et al.

However, while in vivo and in vitro studies have shown that hypoxia may elicit an increase in muscle glucose uptake, studies examining the effects of hypoxia on systemic glucose regulation have been inconsistent Braun et al. Similarly, reduced insulin sensitivity has been reported in healthy men Larsen et al.

While some methodological differences exist between studies, these conflicting findings highlight the complex nature of the processes regulating the systemic glucose R a and R d. In this instance, evidence indicates that acute hypoxic exposure increases the hormonal responses of several glucoregulatory hormones that may augment R a and R d , especially in individuals who are unacclimatized to a hypoxic environment Moncloa et al.

Most prominent among these glucoregulatory hormones is epinephrine; several studies have reported significant increases in epinephrine during hypoxic exposure which coincide with the development of insulin resistance Larsen et al.

In contrast, changes in glucagon, growth hormone and cortisol do not seem to be influenced by hypoxia Larsen et al. However, studies have also observed an increase in cortisol Woods et al. As such, the dissociation between studies showing increased muscle glucose uptake and decreased systemic glucose tolerance following hypoxia could in part, be explained by changes in glucoregulatory hormones.

Exercising in hypoxia compared to normoxia reduces oxygen availability and therefore induces a proportional shift in metabolic pathway flux Davison et al. To compensate for the incomplete oxidation of glucose and reduced ATP-generating efficiency, exercise in hypoxia increases reliance on glucose and glycogen utilization Larsen et al.

Although acute exercise in hypoxia induces a shift towards glucose and glycogen utilization, the subsequent effects on glycaemic control remain unclear De Groote et al.

Mackenzie et al. In a subsequent study, improved insulin sensitivity was observed immediately following exercise in normoxia and hypoxia, although the effects appeared to be sustained 24 h post-exercise only after continuous cycling in hypoxia Mackenzie et al. In contrast, De Groote et al.

Despite exercising at the same relative intensity, cortisol levels during exercise in hypoxia were higher than in normoxia. Key regulators of the glucose transport pathways e. AMPK, TBC1D1 were not reduced immediately after exercise by hypoxia De Groote et al. These results suggest that hypoxia does not impair muscle insulin sensitivity locally, and the acute decrease in systemic glucose tolerance after exercise in hypoxia may be attributed to changes in the glucoregulatory hormones.

Given the systemic effects of hypoxia, it is possible that the interplay of glucoregulatory hormones, including glucagon, catecholamines, GH and incretin hormones could be disrupted, thereby altering glucose homeostasis. The extent of these increases in glucoregulatory hormones, however, depends on the severity and duration of hypoxia as well as the intensity of exercise in hypoxia relative to normoxia absolute vs.

relative intensity. In particular, exercise performed in hypoxia at the same absolute intensity as in normoxia has been shown to exaggerate the increase in epinephrine Cooper et al.

In contrast, submaximal exercise in hypoxia does not seem to alter the responses of catecholamines, glucagon and insulin compared to exercise in normoxia when performed at a similar relative intensity Bouissou et al.

Altogether, the identification of a single candidate hormone e. epinephrine that is altered by the addition of hypoxia to exercise, has so far been unable to account for the differences in acute systemic glucose tolerance Larsen et al.

Rather, it is more likely that several glucoregulatory hormones interact to induce the changes in systemic glucose tolerance Eigler et al. Exercise in hypoxia amplifies many intracellular processes associated with glucose uptake [e. GLUT-4 translocation, increased utilization of glycogen and glucose-derived metabolites Cooper et al.

As such, the glucose R d , at least into the contracting musculature, is expected to be increased. However, the localized increase in glucose uptake may not be reflected in the systemic glucose concentrations since a concomitant increase in the glucose R a via hepatic glucose production and release are expected.

Indeed, a nearly two-fold increase in the glucose R a has been observed in hypoxia versus normoxia Cooper et al. In addition to the effects of glucoregulatory hormones, the glucose R a may also be influenced by circulating metabolites due to a shift in metabolic flux.

Specifically, under hypoxic conditions, plasma triglyceride levels remain unchanged De Groote et al. Additionally, the conversion of pyruvate to lactate is increased Lundby and Van Hall ; Wadley et al. Lactate, being a gluconeogenic substrate, constitutes a prime carbon source for the repletion of blood glucose and consequently muscle glycogen via the Cori cycle, while a proportion of accumulated lactate is also oxidized Fournier et al.

Further research is required to examine the contribution of lactate to glucose R a following exercise in hypoxia. While the regulation of these metabolic pathways may reflect a transient acute response in maintaining metabolic balance to a perturbation induced by hypoxia , longer-term training studies in hypoxia are needed to provide a greater understanding of any underlying metabolic changes.

Findings from studies assessing the effects of exercise training in hypoxia on insulin sensitivity have been inconsistent Haufe et al.

Haufe et al. Additionally, De Groote et al. Importantly, whilst the absolute aerobic workload power output during cycling multiplied by the duration of exercise was lower in hypoxia, both normoxia and hypoxia training-induced similar improvements in insulin sensitivity assessed via HOMA index.

Whether the larger improvements in insulin sensitivity following short-term i. Of note, studies reporting a comparable effect of exercise training on glucose tolerance in hypoxia and normoxia have employed similar relative exercise intensities De Groote et al.

Accordingly, training in hypoxia is performed at a lower absolute intensity than in normoxia, which could be beneficial for individuals who are unable to tolerate high loads imposed on their locomotor system, including comorbidities such as knee osteoarthritis Girard et al.

However, given that the intensity absolute vs. relative of exercise largely influences skeletal muscle AMPK signalling Wadley et al. A key concern associated with hypoxia training is the associated inflammatory response Hosogai et al.

An alteration in oxygen tension in the cells results in the activation of HIF, a key regulator of inflammation and immunity; whether the activation of HIF is pro- or anti-inflammatory in vivo is, however, dependent on the internal environment Scholz and Taylor Additionally, it has also been suggested that hypoxia may trigger endoplasmic reticulum stress Hosogai et al.

That said, acute inflammatory responses are an important physiologic response that functions to restore tissue homeostasis and are required for beneficial adaptations Medzhitov Accordingly, it is chronic or excessive inflammatory responses, that may impair metabolic regulation and that is associated with insulin resistance Petersen and Shulman Further research will need to determine the role of hypoxic training in regulating the pro- and anti-inflammatory responses and the subsequent management of glycaemia in individuals with insulin resistance or T2DM.

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. However, such a framework does not cover the conflicting effects of exercise in hypoxia on glycaemic control Mackenzie et al.

As such, the role of the multiple, integrated systemic responses which regulate glucose tolerance need to be considered. Specifically, the balance between the net tissue glucose uptake and endogenous glucose production and release, are systemically regulated via the central nervous system Güemes and Georgiou , the endocrine system Röder et al.

level of insulin sensitivity , the exercise variables type, duration, intensity and frequency as well as the hypoxic exposure duration, severity of hypoxia, method of implementation [normobaric vs.

hypobaric; intermittent vs. A clinical phenotype of insulin resistance and T2DM is a metabolic dysregulation of lipids, amino acids, and glucose. As such, analysis of the quantitative complement of metabolites in a biological system i.

Indeed, metabolomics i. Molecular phenotyping has emerged as an essential tool in exploring, characterizing, and understanding the dynamic interactions between our genes and environment diet, lifestyle and their phenotypic expression across diverse human populations.

While a wide array of biofluids, tissues and cells can be used in metabolic phenotyping studies, the collection of a blood sample is most frequently performed since it is minimally invasive. Accordingly, this has led to the discovery of biomarkers that may predict the onset and severity of T2DM.

More recently, there has been an increased interest in the use of metabolic profiling approaches to identify molecular transducers mediating the metabolic benefits of exercise Li et al.

Importantly, the identification of mechanistic biomarkers could be used to determine the efficacy of hypoxic training stimulus. Another possible application of metabolomics is the analysis of metabolites associated with glycogen metabolism. As highlighted in this review, the depletion of glycogen following high-intensity exercise is an important factor promoting glucose transport and improving insulin sensitivity Shearer and Graham ; Jensen et al.

Within this context, the discovery of multiple proteins containing glycogen binding domains regions within proteins that allow interactions with glycogen has added increased complexity to the structure and processes regulating glycogen depletion and synthesis McBride and Hardie ; Shearer and Graham ; Philp et al.

The application of metabolomics and proteomics will likely progress our understanding of the processes regulating glycogen depletion and synthesis, including the apparent preservation of a minimum glycogen level in the skeletal muscle, and the link with insulin sensitivity.

A key challenge in hypoxic training is the inter-individual variation in response to hypoxia Soo et al. There is also heterogeneity in the metabolic profile typically measured under fasting condition of individuals with prediabetes Chen et al. This is further complicated by the amplification of inter-individual variations in the metabolic profile when healthy humans are subjected to physiological stress e.

exercise, cold Krug et al. Accordingly, it is tenable to expect inter-individual variations in physiological responses when individuals with prediabetes undergo hypoxic training. In this instance, the use of metabolic profiling using biomarkers that are known to be associated with T2DM may help to discriminate individuals with prediabetes who are at higher risk of developing T2DM, that may require a more intensified training intervention Stefan et al.

Additionally, the hypoxia-induced metabolomic response can be measured to evaluate changes in metabolic profile due to the hypoxic training which may provide an early indicator of possible therapeutic benefits or harm of hypoxia. Systemic glucose regulation is intricately linked to cellular glucose transport, which is mediated by the translocation of glucose transport i.

The increase in glucose transport is not only influenced by insulin but can also be stimulated by muscle contraction. Importantly, glucose transport appears to be influenced by the exercise intensity. Unsurprisingly, high-intensity exercise is now widely accepted and recommended for individuals with T2DM Mendes et al.

While glucose uptake increases in the exercised skeletal muscle tissue, there remains a discrepancy between studies regarding the effects of acute exercise on systemic postprandial glucose tolerance.

This may in part, be explained by different responses in glucoregulatory hormones e. epinephrine, growth hormone, cortisol , which are in turn influenced by the intensity and duration of exercise. The increased rates of glucose uptake disappearance into the skeletal muscle with exercise, may thus have been negated by an increased rate of glucose appearance resulting in either unchanged or worsened systemic glucose concentration.

Accordingly, the role of the multiple, integrated systemic responses which regulate glucose tolerance needs careful consideration to progress current knowledge.

The finding that contraction-induced increase in glucose uptake is not limited to exercise but can also be stimulated by hypoxia Cartee et al.

In this instance, current findings seem to indicate that exercise in hypoxia performed at the same relative intensity i. Hypoxic training may thus be an exercise intervention for individuals who are unable to tolerate high loads. However, further research is required to determine the optimal intensity during hypoxic training.

Inter-individual variability in response to hypoxia may influence the outcomes of hypoxia training. The application of metabolomics presents as a promising approach to optimize hypoxic training by enabling the quantification of the individual metabolic responses to the training intervention and hypoxic stimuli.

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Athletes benefit from knowing how carbohydrates are used by the muscles to Detox and cleansing programs energy Anti-allergic medications under Exercise and glucose metabolism circumstances. Non-athletes and those with metabplism 2 diabetes benefit from learning how Exercise and glucose metabolism can Exercisd their blood sugar and improve their quality of life. Skeletal muscle mftabolism one of the primary anv of carbohydrates as glucose to generate energy in the form of ATP adenosine triphosphate to fuel movement. This is especially true for higher intensity exercise, when skeletal muscle seems to favor sugar to generate quick energy as opposed to fat. Carbohydrate depletion is associated with fatigue and reduced performance in athletes. It is important for athletes to consume adequate amounts of carbohydrates to avoid fatigue and poor performance. Many endurance athletes, like long distance runners, even do carbohydrate loading by eating many carbohydrate-rich food days before a big event to increase their muscle glycogen stores. Thank Detox and cleansing programs for Glucose normalization nature. Immunity defense mechanisms are using Exercise and glucose metabolism browser version metbolism limited support for CSS. To metabo,ism the best experience, we recommend you Exercisr a more gucose to date browser or turn Exerciwe compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Exercise-stimulated signal transduction can restore glucose metabolism in insulin-resistant muscle through both acute activation of glucose transport and by improving insulin sensitivity for up to 48 hours after exercise. Glucose is a major fuel source during exercise and glucose uptake by skeletal muscle can increase by up to fold during bouts of exercise.

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What happens to your blood sugar when you work out?