Seven days of bed rest decrease insulin action on glucose uptake in leg and whole body

Impaired glucose tolerance develops in normal humans after short-term bed rest. To elucidate the mechanism, insulin action on whole body glucose uptake rate (WBGUR) and leg glucose uptake rate (LGUR) was measured by sequential euglycemic clamp technique combined with femoral arterial and venous cannulation at insulin concentrations of 10 +/- 1, 18 +/- 1, 37 +/- 2, and 360 +/- 15 microU/ml. Studies were performed before (C) and after (BR) 7 days of strict bed rest. WBGUR was significantly lower after bed rest than before (5.5 +/- 0.4 and 7.2 +/- 0.8 mg.min-1.kg-1, respectively) when insulin was 37 microU/ml. LGUR was even more markedly depressed by bed rest, being 0.6 +/- 0.1, 0.9 +/- 0.2, and 2.8 +/- 0.4 mg.min-1.kg leg-1 (BR) compared with 0.9 +/- 0.1, 1.7 +/- 0.4, and 5.9 +/- 0.5 mg.min-1.kg leg-1 (C) (P less than 0.05) at the three lower insulin concentrations. At these insulin concentrations also, lactate release and glucose oxidation and glycogen storage estimated by indirect calorimetry were lower in the leg after bed rest. At the highest insulin dose WBGUR was similar on BR and C days, while LGUR was lower after bed rest. In conclusion, 7 days of bed rest decrease whole body insulin action, a fact that is explained by decreased insulin action in inactive muscle.

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Effect of training on the dose-response relationship for insulin action in men

Journal of Applied Physiology ◽

10.1152/jappl.1989.66.2.695 ◽

1989 ◽

Vol 66 (2) ◽

pp. 695-703 ◽

Cited By ~ 71

Author(s):

K. J. Mikines ◽

B. Sonne ◽

P. A. Farrell ◽

B. Tronier ◽

H. Galbo

Keyword(s):

Glucose Uptake ◽

Insulin Action ◽

Glycogen Synthase ◽

Vastus Lateralis ◽

Training Session ◽

Glycogen Storage ◽

Whole Body ◽

Vastus Lateralis Muscle ◽

Trained Subjects ◽

Insulin Responsiveness

Seven endurance-trained subjects [maximal O2 consumption (VO2max) 64 +/- 1 (SE) ml.min-1.kg-1] were subjected to three sequential hyperinsulinemic euglycemic clamps 15 h after having performed their last training session (T). Results were compared with findings in seven untrained subjects (VO2max 44 +/- 2 ml.min-1.kg-1) studied both at rest (UT) and after 60 min of bicycle exercise at 150 W (UT-ex). In T and UT-ex compared with UT, sensitivity for insulin-mediated whole-body glucose uptake was higher [insulin concentrations eliciting half-maximal glucose uptake being 44 +/- 2 (T) and 43 +/- 4 (UT-ex) vs. 52 +/- 3 microU/ml (UT), P less than 0.05] and responsiveness was higher [13.4 +/- 1.2 (T) and 10.9 +/- 0.7 (UT-ex) vs. 9.5 +/- 0.7 mg.min-1.kg-1 (UT), P less than 0.05]. Furthermore, responsiveness was higher (P less than 0.05) in T than in UT-ex. Insulin-stimulated O2 uptake and maximal glucose oxidation rate were higher in T than in UT and UT-ex. Insulin-stimulated conversion or glucose to glycogen and muscle glycogen synthase was higher in T than in UT and UT-ex. However, glycogen storage in vastus lateralis muscle was found only in UT-ex. No change in any glucoregulatory hormone or metabolite could explain the increased insulin action in trained subjects. It is concluded that physical training induces an adaptive increase in insulin responsiveness of whole-body glucose uptake, which does not reflect increased glycogen deposition in muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

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Antihyperglycemic and Antilipidemic Effects of the Ethanol Extract Mixture of Ligularia fischeri and Momordica charantia in Type II Diabetes-Mimicking Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/3468040 ◽

2018 ◽

Vol 2018 ◽

pp. 1-15

Author(s):

Hyun Jin Baek ◽

Yong Joon Jeong ◽

Jeong Eun Kwon ◽

Jong Sung Ra ◽

Sung Ryul Lee ◽

...

Keyword(s):

Glucose Uptake ◽

Uptake Rate ◽

Glucose Transporter ◽

Synergistic Effects ◽

Momordica Charantia ◽

C2c12 Cells ◽

Peroxisome Proliferator ◽

Glucose Uptake Rate ◽

Ligularia Fischeri

The extract of the Momordica charantia fruit (MCE) is recognized as an alternative treatment for diabetes. The extract of Ligularia fischeri leaves (LFE) is traditionally used as a folk medicine for treating inflammatory diseases in Korea as well. In this study, we investigated the synergistic effect of MCE combined with LFE on antihyperglycemic and antihyperlipidemic potentials. Based on the α-glucosidase inhibitory effect and promotion of adipocyte differentiation in the 3T3-L1 cell line, the MLM was prepared with MCE:LFE (8:2 weight:weight). MLM showed the synergistic effects in the promotion of the glucose uptake rate, suppression of dipeptidyl peptidase-4 (DPP-4) mRNA expression, upregulation of an insulin receptor substrate and glucose transporter type-4 expression, and an increase in insulin-associated signaling in C2C12 cells. In addition, the efficacy of peroxisome proliferator-activated receptor-γ agonism and glucose uptake rate by MLM supplementation was significantly enhanced in vitro. Then, the antihyperglycemic and antihyperlipidemic effects of MCE, LFE, and MLM at the dose of 50, 100, and 200 mg/kg/day (n = 6 per each group) were determined in streptozotocin (STZ)-insulted mice fed an atherogenic diet (ATH) for 4 weeks. In addition, MLM (50, 100, and 200 mg/kg/day, n = 5 per each group) was supplemented in ATH-fed db/db mice for 10 weeks. Compared with MCE or LFE alone, MLM supplementation led to a more significant reduction of glucose levels in both STZ/ATH and db/db/ATH mice as well as lowered lipid profiles in STZ/ATH mice. In addition, the stimulation of islet of Langerhans regeneration was more pronounced by MLM supplementation in both mice models. In conclusion, antihyperglycemic and antihyperlipidemic effects were strengthened by the combined extracts of L. fischeri and M. charantia (MLM) in diabetes-mimicking mice.

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Mechanisms underlying absent training-induced improvement in insulin action in lean, hyperandrogenic women with polycystic ovary syndrome (PCOS)

10.2337/figshare.12860540 ◽

2020 ◽

Author(s):

Ada Admin ◽

Solvejg L. Hansen ◽

Kirstine N. Bojsen-Møller ◽

Anne-Marie Lundsgaard ◽

Frederikke L. Hendrich ◽

...

Keyword(s):

Skeletal Muscle ◽

Blood Flow ◽

Exercise Training ◽

Polycystic Ovary Syndrome ◽

Glucose Uptake ◽

Insulin Action ◽

Polycystic Ovary ◽

Whole Body ◽

Ovary Syndrome ◽

Leg Blood Flow

Women with polycystic ovary syndrome (PCOS) have been shown to be less insulin sensitive compared with control women, independent of BMI. Training is associated with molecular adaptations in skeletal muscle improving glucose uptake and metabolism in both healthy and type 2 diabetic individuals. In the present study, lean, hyperandrogenic women with PCOS (n=9) and healthy controls (CON, n=9) completed 14 weeks of controlled and supervised exercise training. In CON, the training intervention increased whole body insulin action by 26% and insulin-stimulated leg glucose uptake by 53%, together with increased insulin-stimulated leg blood flow and a more oxidative muscle fiber type distribution. In PCOS, no such changes were found, despite similar training intensity and improvements in maximal oxygen uptake. In skeletal muscle of CON, but not PCOS, training increased GLUT4 and HKII mRNA and protein expressions. These data suggest that the impaired increase in whole body insulin action in women with PCOS with training is caused by an impaired ability to upregulate key glucose handling proteins for insulin-stimulated glucose uptake in skeletal muscle, and insulin-stimulated leg blood flow. Still, other important benefits of exercise training appeared in women with PCOS, including an improvement of the hyperandrogenic state.

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Reduced malonyl-CoA content in recovery from exercise correlates with improved insulin-stimulated glucose uptake in human skeletal muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.90556.2008 ◽

2009 ◽

Vol 296 (4) ◽

pp. E787-E795 ◽

Cited By ~ 15

Author(s):

Christian Frøsig ◽

Carsten Roepstorff ◽

Nina Brandt ◽

Stine J. Maarbjerg ◽

Jesper B. Birk ◽

...

Keyword(s):

Glucose Uptake ◽

Insulin Action ◽

Acute Exercise ◽

Glycogen Synthase ◽

Knee Extensor ◽

Human Muscle ◽

Whole Body ◽

Euglycemic Hyperinsulinemic Clamp ◽

Malonyl Coa ◽

Before And After

This study evaluated whether improved insulin-stimulated glucose uptake in recovery from acute exercise coincides with reduced malonyl-CoA (MCoA) content in human muscle. Furthermore, we investigated whether a high-fat diet [65 energy-% (Fat)] would alter the content of MCoA and insulin action compared with a high-carbohydrate diet [65 energy-% (CHO)]. After 4 days of isocaloric diet on two occasions (Fat/CHO), 12 male subjects performed 1 h of one-legged knee extensor exercise (∼80% peak workload). Four hours after exercise, insulin-stimulated glucose uptake was determined in both legs during a euglycemic-hyperinsulinemic clamp. Muscle biopsies were obtained in both legs before and after the clamp. Four hours after exercise, insulin-stimulated glucose uptake was improved (∼70%, P < 0.001) independent of diet composition and despite normal insulin-stimulated regulation of insulin receptor substrate-1-associated phosphatidylinositol 3-kinase, Akt, GSK-3, and glycogen synthase. Interestingly, exercise resulted in a sustained reduction (∼20%, P < 0.05) in MCoA content 4 h after exercise that correlated ( r = 0.65, P < 0.001) with improved insulin-stimulated glucose uptake. Four days of Fat diet resulted in an increased content of intramyocellular triacylglycerol ( P < 0.01) but did not influence muscle MCoA content or whole body insulin-stimulated glucose uptake. However, at the muscular level proximal insulin signaling and insulin-stimulated glucose uptake appeared to be compromised, although to a minor extent, by the Fat diet. Collectively, this study indicates that reduced muscle MCoA content in recovery from exercise may be part of the adaptive response leading to improved insulin action on glucose uptake after exercise in human muscle.

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Short-term K+ deprivation provokes insulin resistance of cellular K+ uptake revealed with the K+ clamp

AJP Renal Physiology ◽

10.1152/ajprenal.2001.280.1.f95 ◽

2001 ◽

Vol 280 (1) ◽

pp. F95-F102 ◽

Cited By ~ 35

Author(s):

Cheol S. Choi ◽

Curtis B. Thompson ◽

Patrick K. K. Leong ◽

Alicia A. McDonough ◽

Jang H. Youn

Keyword(s):

Insulin Resistance ◽

Atpase Activity ◽

Infusion Rate ◽

Insulin Action ◽

Insulin Dose ◽

Short Term ◽

Conscious Rat ◽

Physiological Concentration ◽

Glucose Clearance

We aimed to test the feasibility of quantifying insulin action on cellular K+ uptake in vivo in the conscious rat by measuring the exogenous K+ infusion rate needed to maintain constant plasma K+ concentration ([K+]) during insulin infusion. In this “K+ clamp” the K+ infusion rate required to clamp plasma [K+] is a measure of insulin action to increase net plasma K+ disappearance. K+ infusion rate required to clamp plasma [K+] was insulin dose dependent. Renal K+ excretion was not significantly affected by insulin at a physiological concentration (∼90 μU/ml, P > 0.05), indicating that most of insulin-mediated plasma K+ disappearance was due to K+ uptake by extrarenal tissues. In rats deprived of K+ for 2 days, plasma [K+] fell from 4.2 to 3.8 mM, insulin-mediated plasma glucose clearance was normal, but insulin-mediated plasma K+ disappearance decreased to 20% of control, even though there was no change in muscle Na-K-ATPase activity or expression, which is believed to be the main K+ uptake route. After 10 days K+ deprivation, plasma [K+] fell to 2.9 mM, insulin-mediated K+ disappearance decreased to 6% of control (glucose clearance normal), and there were 50% decreases in Na-K-ATPase activity and α2-subunit levels. In conclusion, the present study proves the feasibility of the K+ clamp technique and demonstrates that short-term K+ deprivation leads to a near complete insulin resistance of cellular K+uptake that precedes changes in muscle sodium pump expression.

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Effect of Flow Rate and Glucose Concentration on Glucose Uptake Rate by the Rat Limb

Experimental Biology and Medicine ◽

10.3181/00379727-154-39597 ◽

1977 ◽

Vol 154 (1) ◽

pp. 33-36 ◽

Cited By ~ 21

Author(s):

B. Grubb ◽

J. F. Snarr

Keyword(s):

Glucose Uptake ◽

Flow Rate ◽

Uptake Rate ◽

Glucose Concentration ◽

Glucose Uptake Rate

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TNF-α acutely inhibits vascular effects of physiological but not high insulin or contraction

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00119.2003 ◽

2003 ◽

Vol 285 (3) ◽

pp. E654-E660 ◽

Cited By ~ 40

Author(s):

Lei Zhang ◽

Catherine M. Wheatley ◽

Stephen M. Richards ◽

Eugene J. Barrett ◽

Michael G. Clark ◽

...

Keyword(s):

Insulin Resistance ◽

Muscle Contraction ◽

Glucose Uptake ◽

Capillary Flow ◽

Insulin Dose ◽

Whole Body ◽

Vascular Effects ◽

Capillary Recruitment ◽

Tnf Α

TNF-α is elevated in many states of insulin resistance, and acutely administered TNF-α in vivo inhibits insulin-mediated hemodynamic effects and glucose uptake in muscle. In this study, we assess whether the inhibitory effects of TNF-α are affected by insulin dose or muscle contraction. Whole body glucose infusion rate (GIR), femoral blood flow (FBF), hindleg vascular resistance, hindleg glucose uptake (HGU), 2-deoxyglucose uptake into muscles of the lower leg (R′g) and hindleg metabolism of infused 1-methylxanthine (1-MX), a measure of capillary recruitment, were determined. Three groups were studied with and without infusion of TNF-α: euglycemic insulin-clamped, one-leg field-stimulated (2 Hz, 0.1 ms at 30 V), and saline-infused control anesthetized rats. Insulin infusions were 3, 10, or 30 mU · kg-1 · min-1 for 2 h. 1-MX metabolism was maximally increased by all three doses of insulin. GIR, HGU, and R′g were maximal at 10 mU and FBF was maximal at 30 mU of insulin. Contraction increased FBF, HGU, and 1-MX. TNF-α (0.5 μg · kg-1 · h-1) totally blocked the 3 and 10 mU insulin-mediated increases in FBF and 1-MX, and partly blocked GIR, HGU, and R′g. None of the increases due to twitch contraction was affected by TNF-α, and only the increase in FBF due to 30 mU of insulin was partly affected. We conclude that muscle capillary recruitment and glucose uptake due to high levels of insulin or muscle contraction under twitch stimuli at 2 Hz are resistant to TNF-α. These findings may have implications for ameliorating muscle insulin resistance resulting from increased plasma TNF-α and for the differing mechanisms by which contraction and insulin recruit capillary flow in muscle.

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Whole body and regional body composition changes following 10-day hypoxic confinement and unloading–inactivity

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2013-0278 ◽

2014 ◽

Vol 39 (3) ◽

pp. 386-395 ◽

Cited By ~ 16

Author(s):

Tadej Debevec ◽

Adam C. McDonnell ◽

Ian A. Macdonald ◽

Ola Eiken ◽

Igor B. Mekjavic

Keyword(s):

Body Composition ◽

Energy Intake ◽

Body Mass ◽

Bed Rest ◽

Whole Body ◽

Short Term ◽

X Ray ◽

Regional Body Composition ◽

Before And After ◽

Composition Changes

Future planetary habitats will expose inhabitants to both reduced gravity and hypoxia. This study investigated the effects of short-term unloading and normobaric hypoxia on whole body and regional body composition (BC). Eleven healthy, recreationally active, male participants with a mean (SD) age of 24 (2) years and body mass index of 22.4 (3.2) kg·m−2 completed the following 3 10-day campaigns in a randomised, cross-over designed protocol: (i) hypoxic ambulatory confinement (HAMB; FIO2 = 0.147 (0.008); PIO2 = 93.8 (0.9) mm Hg), (ii) hypoxic bed rest (HBR; FIO2 = 0.147 (0.008); PIO2 = 93.8 (0.9) mm Hg), and (iii) normoxic bed rest (NBR; FIO2 = 0.209; PIO2 = 133.5 (0.7) mm Hg). Nutritional requirements were individually precalculated and the actual intake was monitored throughout the study protocol. Body mass, whole body, and regional BC were assessed before and after the campaigns using dual-energy X-ray absorptiometry. The calculated daily targeted energy intake values were 2071 (170) kcal for HBR and NBR and 2417 (200) kcal for HAMB. In both HBR and NBR campaigns the actual energy intake was within the targeted level, whereas in the HAMB the intake was lower than targeted (–8%, p < 0.05). Body mass significantly decreased in all 3 campaigns (–2.1%, –2.8%, and –2.0% for HAMB, HBR, and NBR, respectively; p < 0.05), secondary to a significant decrease in lean mass (–3.8%, –3.8%, –4.3% for HAMB, HBR, and NBR, respectively; p < 0.05) along with a slight, albeit not significant, increase in fat mass. The same trend was observed in the regional BC regardless of the region and the campaign. These results demonstrate that, hypoxia per se, does not seem to alter whole body and regional BC during short-term bed rest.

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