Myocardial and skeletal muscle glucose uptake during exercise in humans

Kemppainen, Jukka; Fujimoto, Toshiaki; Kalliokoski, Kari K.; Viljanen, Tapio; Nuutila, Pirjo; Knuuti, Juhani

doi:10.1113/jphysiol.2002.018135

Cited by 115 publications

(127 citation statements)

References 33 publications

Supporting

Mentioning

111

Contrasting

Order By: Relevance

“…[ 18 F]Fluorodeoxyglucose (FDG) is retained within the cell and can be quantified using PET [33]. FDG (5 MBq/kg) was injected 10 min post exercise initiation and exercise proceeded for an additional 20 min [34,35]. Blood samples were taken for metabolite analysis immediately prior to FDG injection, and at 20 and 60 min post-injection.…”

Section: Exercise Intervention and [ 18 F]fluorodeoxyglucose Petmentioning

confidence: 99%

Naturally occurring R225W mutation of the gene encoding AMP-activated protein kinase (AMPK)γ3 results in increased oxidative capacity and glucose uptake in human primary myotubes

et al. 2010

View full text Add to dashboard Cite

Aims/hypothesis AMP-activated protein kinase (AMPK) has a broad role in the regulation of glucose and lipid metabolism making it a promising target in the treatment of type 2 diabetes mellitus. We therefore sought to characterise for the first time the effects of chronic AMPK activation on skeletal muscle carbohydrate metabolism in carriers of the rare gain-of-function mutation of the gene encoding AMPKγ 3 subunit, PRKAG3 R225W.Methods Aspects of fuel metabolism were studied in vitro in myocytes isolated from vastus lateralis of PRKAG3 R225W carriers and matched control participants. In vivo, muscular strength and fatigue were evaluated by isokinetic dynamometer and surface electromyography, respectively. Glucose uptake in exercising quadriceps was determined using [ 18 F]fluorodeoxyglucose and positron emission tomography. Results Myotubes from PRKAG3 R225W carriers had threefold higher mitochondrial content (p < 0.01) and oxidative capacity, higher leak-dependent respiration (1.6-fold, p<0.05), higher basal glucose uptake (twofold, p<0.01) and higher glycogen synthesis rates (twofold, p<0.05) than control myotubes. They also had higher levels of intracellular glycogen (p<0.01) and a trend for lower intramuscular triacylglycerol stores. R225W carriers showed remarkable resistance to muscular fatigue and a trend for increased glucose uptake in exercising muscle in vivo. Conclusions/interpretation Through the enhancement of skeletal muscle glucose uptake and increased mitochondrial content, the R225W mutation may significantly enhance exercise performance. These findings are also consistent with the hypothesis that the γ 3 subunit of AMPK is a promising tissue-specific target for the treatment of type 2 diabetes mellitus, a condition in which glucose uptake and mitochondrial function are impaired.

show abstract

Section: Exercise Intervention and [ 18 F]fluorodeoxyglucose Petmentioning

confidence: 99%

Naturally occurring R225W mutation of the gene encoding AMP-activated protein kinase (AMPK)γ3 results in increased oxidative capacity and glucose uptake in human primary myotubes

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Clearly, this is not the case in vivo where resting lactate levels are Ϸ1 mmol/L and can easily reach Ն5 mmol/L in response to exercise, trauma, or stress. 22,23 As shown in Table 2, both lactate and pyruvate contribute significantly to oxidative ATP production. It is noteworthy that even though lactate is present at a 5-fold-lower concentration than glucose in the control group, its contribution to ATP production is Ͼ3-fold higher.…”

Section: Wang Et Al Cardiac Metabolism and Function After Ischemia 2069mentioning

confidence: 99%

Impact of High Glucose/High Insulin and Dichloroacetate Treatment on Carbohydrate Oxidation and Functional Recovery After Low-Flow Ischemia and Reperfusion in the Isolated Perfused Rat Heart

Wang¹,

Lloyd²,

Chatham³

2005

Circulation

View full text Add to dashboard Cite

Background-It is believed that increasing cardiac glucose metabolism in the setting of ischemia and reperfusion is protective because of the resulting decrease in fatty acid oxidation, which improves cardiac efficiency and increases glucose oxidation relative to glycolysis; however, these conclusions are based primarily on studies in which glucose is the only carbohydrate provided. The goal of this study was to examine the effect of stimulating myocardial carbohydrate use either by increasing glucose and insulin levels or by using dichloroacetate on the response to ischemia and reperfusion in hearts perfused with physiological concentrations of lactate and pyruvate plus glucose and fatty acids. Methods and Results-Metabolic fluxes were determined in hearts from male Sprague-Dawley rats perfused with 13 C-labeled substrates using 13 C/ 1 H-NMR isotopomer analysis after 30 minutes of low-flow ischemia (0.3 mL/min) and 60 minutes of reperfusion. Measurements were made under control conditions: 5 mmol/L glucose, 1 mmol/L lactate, 0.1 mmol/L pyruvate, 0.3 mmol/L palmitate, and 50 U/mL insulin plus dichloroacetate 5 mmol/L or glucose and insulin increased to 30 mmol/L and 1000 U/mL, respectively. Dichloroacetate increased carbohydrate oxidation and the ratio of glucose oxidation to glycolysis but did not improve functional recovery or cardiac efficiency; however, elevated glucose and insulin levels improved functional recovery and cardiac efficiency but did not increase carbohydrate oxidation or the ratio of glucose oxidation to glycolysis. Conclusions-These data support the notion that increasing myocardial glucose use is beneficial in the setting of ischemia and reperfusion; however, the protective effect appears not to be mediated by shifting the balance between carbohydrate and fatty acid oxidation.

show abstract

“…This is despite the fact that the myocardium is capable of utilizing a wide variety of fuels for oxidative energy production. At rest, circulating lactate concentrations are ϳ1 mM (Table 1) and during moderate exercise can easily reach up to 3-5 mM (37). More than 20 years ago, Drake et al (20) showed that the uptake of lactate by the heart in vivo is directly proportional to its serum concentration.…”

mentioning

confidence: 99%

Differential modulation of glucose, lactate, and pyruvate oxidation by insulin and dichloroacetate in the rat heart

Lloyd¹,

Brocks²,

Chatham³

2003

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Despite the fact that lactate and pyruvate are potential substrates for energy production in vivo, our understanding of the control and regulation of carbohydrate metabolism is based principally on studies where glucose is the only available carbohydrate. Therefore, the purpose of this study was to determine the contributions of lactate, pyruvate, and glucose to energy production in the isolated, perfused rat heart over a range of insulin concentrations and after activation of pyruvate dehydrogenase with dichloroacetate (DCA). Hearts were perfused with physiological concentrations of [1-13 C]glucose, [U-13 C]lactate, [2-13 C]-pyruvate, and unlabeled palmitate for 45 min. Hearts were freeze clamped, and 13 C NMR glutamate isotopomer analysis was performed on tissue extracts. Glucose, lactate, and pyruvate all contributed significantly to myocardial energy production; however, in the absence of insulin, glucose contributed only 25-30% of total pyruvate oxidation. Even under conditions where carbohydrates represented Ͼ95% of substrate entering the tricarboxylic acid (TCA) cycle, we found that glucose contributed at most 50-60% of total carbohydrate oxidation. Despite being present at only 0.1 mM, pyruvate contributed between ϳ10% and 30% of total acetyl-CoA entry into the TCA cycle. We also found that insulin and DCA not only increased glucose oxidation but also exogenous pyruvate oxidation; however, lactate oxidation was not increased. The differential effects of insulin and DCA on pyruvate and lactate oxidation provide further evidence for compartmentation of cardiac carbohydrate metabolism. These results may have important implications for understanding the mechanisms underlying the beneficial effects of increasing cardiac carbohydrate metabolism. substrate metabolism; carbohydrates; fatty acids THE PREVAILING VIEW of cardiac energy production is that long-chain fatty acids are the primary oxidative energy source, followed to a lesser extent by glucose use, with other substrates such as lactate playing a much smaller role. This is despite the fact that the myocardium is capable of utilizing a wide variety of fuels for oxidative energy production. At rest, circulating lactate concentrations are ϳ1 mM (Table 1) and during moderate exercise can easily reach up to 3-5 mM (37). More than 20 years ago, Drake et al. (20) showed that the uptake of lactate by the heart in vivo is directly proportional to its serum concentration. In addition, it has been shown that in the isolated perfused heart, lactate contributes significantly to acetyl-CoA formation, often contributing more than glucose (9,10,35). In addition, serum pyruvate is typically in the range of 0.1-0.2 mM (Table 1), and, while this is relatively low, pyruvate is readily taken up and oxidized by the heart (36, 40, 45) and thus could contribute significantly to overall oxidative energy production in vivo.There is a resurgence of interest in the regulation of cardiac metabolism, driven, at least in part, by the manipulation of cardiac metabolism as a potential ...

show abstract

Myocardial and skeletal muscle glucose uptake during exercise in humans

Cited by 115 publications

References 33 publications

Naturally occurring R225W mutation of the gene encoding AMP-activated protein kinase (AMPK)γ3 results in increased oxidative capacity and glucose uptake in human primary myotubes

Naturally occurring R225W mutation of the gene encoding AMP-activated protein kinase (AMPK)γ3 results in increased oxidative capacity and glucose uptake in human primary myotubes

Impact of High Glucose/High Insulin and Dichloroacetate Treatment on Carbohydrate Oxidation and Functional Recovery After Low-Flow Ischemia and Reperfusion in the Isolated Perfused Rat Heart

Differential modulation of glucose, lactate, and pyruvate oxidation by insulin and dichloroacetate in the rat heart

Contact Info

Product

Resources

About