Effect of hypothermia on 2-deoxy-glucose transport, insulin binding and insulin sensitivity of the rat soleus muscle

To determine the effect of desensitization of adipocyte beta-adrenergic receptors on insulin sensitivity, rats were continuously infused with isoproterenol (50 or 100 micrograms.kg-1.h-1) for 3 days by osmotic minipumps. Epididymal adipocytes were isolated. The cells from treated animals were desensitized to isoproterenol, as determined by response of lipolysis (glycerol release). Binding of [125I]iodocyanopindolol was decreased by approximately 80% in adipocyte plasma membranes isolated from treated rats, indicating that beta-adrenergic receptors were downregulated. Cellular concentrations of Gn alpha and Gi alpha were not altered. Insulin sensitivity was determined by measuring the effect of insulin on glucose transport (2-deoxy-[3H]glucose uptake). Cells from the isoproterenol-infused rats were markedly more sensitive to insulin than those from control rats. This was evidenced by an approximately 50% increase in maximal glucose transport rate in cells from the high-dose isoproterenol-treated rats and by an approximately 40% decrease in the half-maximal effective concentration of insulin in both groups. 125I-labeled insulin binding to adipocytes was not altered by the isoproterenol infusions, indicating that desensitization of beta-adrenergic receptors results in tighter coupling between insulin receptors and stimulation of glucose transport.

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Furosemide decreases the sensitivity of glucose transport to insulin in skeletal muscle in vitro

Acta Endocrinologica ◽

10.1530/eje.0.1390118 ◽

1998 ◽

Vol 139 (1) ◽

pp. 118-122 ◽

Cited By ~ 3

Author(s):

G Dimitriadis ◽

B Leighton ◽

M Parry-Billings ◽

C Tountas ◽

S Raptis ◽

...

Keyword(s):

Skeletal Muscle ◽

Glucose Transport ◽

Soleus Muscle ◽

Transport Process ◽

Glucose Utilization ◽

Glucose Disposal ◽

Rat Soleus Muscle ◽

Lactate Formation

The effects of the diuretic furosemide on the sensitivity of glucose disposal to insulin were investigated in rat soleus muscle in vitro. At basal levels of insulin, the rates of 3-O-methylglucose transport, 2-deoxyglucose phosphorylation and lactate formation were not affected significantly by furosemide (0.5 mmol/l). However, furosemide significantly decreased these rates at physiological and maximal levels of insulin. The contents of 2-deoxyglucose and glucose 6-phosphate in the presence of furosemide were not significantly different from those in control muscles at all levels of insulin studied. It is concluded that furosemide decreases the sensitivity of glucose utilization to insulin in skeletal muscle by directly inhibiting the glucose transport process.

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Effects of insulin and epinephrine on Na+-K+ and glucose transport in soleus muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1987.252.4.e492 ◽

1987 ◽

Vol 252 (4) ◽

pp. E492-E499 ◽

Cited By ~ 11

Author(s):

T. Clausen ◽

J. A. Flatman

Keyword(s):

Glucose Transport ◽

Soleus Muscle ◽

Sugar Transport ◽

Resting Membrane Potential ◽

Exchange System ◽

Glucose Transport System ◽

Rat Soleus Muscle ◽

Possible Cause ◽

K Transport ◽

Stimulation Of

To identify possible cause-effect relationships between changes in active Na+-K+ transport, resting membrane potential, and glucose transport, the effects of insulin and epinephrine were compared in rat soleus muscle. Epinephrine, which produced twice as large a hyperpolarization as insulin, induced only a modest increase in sugar transport. Ouabain, at a concentration (10(-3) M) sufficient to block active Na+-K+ transport and the hyperpolarization induced by the two hormones, did not interfere with sugar transport stimulation. After Na+ loading in K+-free buffer, the return to K+-containing standard buffer caused marked stimulation of active Na+-K+ transport, twice the hyperpolarization produced by insulin but no change in sugar transport. The insulin-induced activation of the Na+-K+ pump leads to decreased intracellular Na+ concentration and hyperpolarization, but none of these events can account for the concomitant activation of the glucose transport system. The stimulating effect of insulin on active Na+-K+ transport was not suppressed by amiloride, indicating that in intact skeletal muscle it is not elicited by a primary increase in Na+ influx via the Na+/H+-exchange system.

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Effect of prolonged anaerobiosis on 125I-insulin binding to rat soleus muscle: permissive effect of ATP.

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1978.235.6.e606 ◽

1978 ◽

Vol 235 (6) ◽

pp. E606

Author(s):

K T Yu ◽

M K Gould

Keyword(s):

Membrane Protein ◽

Soleus Muscle ◽

Specific Binding ◽

High Capacity ◽

Insulin Binding ◽

High Affinity ◽

Dependent Process ◽

Xylose Uptake ◽

High Affinity Site ◽

Rat Soleus Muscle

The specific binding of 125I-insulin by rat soleus muscle was depressed when muscle ATP was depleted, either by prolonged anoxia or more rapidly with 2,4-dinitrophenol. Insulin binding was not eliminated in ATP-depleted muscle, but was reduced by 70--80%. Insulin binding by aerobic muscle could be resolved into two components; a high-affinity, low-capacity site (KD = 7.8 nM) and a low-affinity, high-capacity site (KD = 390 nM). The stimulatory effect of insulin on xylose uptake could be correlated with binding to the high-affinity site. These results indicate that there is some ATP-dependent process involved in the regulation of insulin binding by soleus muscle. It is suggested that this could be a phosphorylation-dephosphorylation system, acting either on the receptor itself or on some closely related membrane protein.

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Insulin sensitivity in adipocytes from subjects with varying degrees of glucose tolerance

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1986.251.3.e306 ◽

1986 ◽

Vol 251 (3) ◽

pp. E306-E310

Author(s):

J. E. Foley ◽

P. Thuillez ◽

S. Lillioja ◽

J. Zawadzki ◽

C. Bogardus

Keyword(s):

Insulin Sensitivity ◽

Glucose Tolerance ◽

Glucose Transport ◽

Insulin Binding ◽

Normal Glucose Tolerance ◽

Dependent Diabetes Mellitus ◽

Oral Glucose ◽

Pima Indians ◽

Wide Range

Previous studies showed that the sensitivity of glucose transport to insulin is lower in adipocytes isolated from subjects with noninsulin-dependent diabetes mellitus and impaired glucose tolerance compared with subjects with normal glucose tolerance. This study analyzed the relationship between insulin sensitivity of glucose transport and glycemia in a large group of nondiabetic-nonglucose-intolerant subjects with a wide range of glycemic response to oral glucose. Seventy-four Pima Indians with 2-h postglucose load glucoses between 77 and 197 mg/100 ml, fasting plasma glucoses between 76 and 108 mg/100 ml, and no postload glucoses less than 199 mg/100 ml were studied. Isolated adipocytes were prepared in vitro after an abdominal fat biopsy, ED50 of insulin for glucose transport was correlated with 2-h postload glucoses, but not between insulin binding per cell or per cell surface area or in ED50 of insulin for antilipolysis and 2-h postglucose load glucoses. Although only 17% of the variation in glucose tolerance could be explained by a change in the sensitivity of glucose transport to insulin, the data suggests that a postinsulin-binding defect in the coupling of insulin binding to glucose transport may be an early step in the development of insulin resistance in human adipocytes.

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Contraction- and hypoxia-stimulated glucose transport is mediated by a Ca2+-dependent mechanism in slow-twitch rat soleus muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00561.2004 ◽

2005 ◽

Vol 288 (6) ◽

pp. E1062-E1066 ◽

Cited By ~ 89

Author(s):

David C. Wright ◽

Paige C. Geiger ◽

John O. Holloszy ◽

Dong-Ho Han

Keyword(s):

Glucose Transport ◽

Soleus Muscle ◽

Fold Increase ◽

High Energy ◽

Muscle Contractions ◽

High Energy Phosphates ◽

Dependent Protein ◽

Rat Soleus Muscle ◽

Slow Twitch ◽

Dependent Mechanism

Increases in contraction-stimulated glucose transport in fast-twitch rat epitrochlearis muscle are mediated by AMPK- and Ca2+/calmodulin-dependent protein kinase (CAMK)-dependent signaling pathways. However, recent studies provide evidence suggesting that contraction-stimulated glucose transport in slow-twitch skeletal muscle is mediated through an AMPK-independent pathway. The purpose of the present study was to test the hypothesis that contraction-stimulated glucose transport in rat slow-twitch soleus muscle is mediated by an AMPK-independent/Ca2+-dependent pathway. Caffeine, a sarcoplasmic reticulum (SR) Ca2+-releasing agent, at a concentration that does not cause muscle contractions or decreases in high-energy phosphates, led to an ∼2-fold increase in 2-deoxyglucose (2-DG) uptake in isolated split soleus muscles. This increase in glucose transport was prevented by the SR calcium channel blocker dantrolene and the CAMK inhibitor KN93. Conversely, 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), an AMPK activator, had no effect on 2-DG uptake in isolated split soleus muscles yet resulted in an ∼2-fold increase in the phosphorylation of AMPK and its downstream substrate acetyl-CoA carboxylase. The hypoxia-induced increase in 2-DG uptake was prevented by dantrolene and KN93, whereas hypoxia-stimulated phosphorylation of AMPK was unaltered by these agents. Tetanic muscle contractions resulted in an ∼3.5-fold increase in 2-DG uptake that was prevented by KN93, which did not prevent AMPK phosphorylation. Taken in concert, our results provide evidence that hypoxia- and contraction-stimulated glucose transport is mediated entirely through a Ca2+-dependent mechanism in rat slow-twitch muscle.

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Glucose uptake and insulin sensitivity in rat muscle: changes during 3-96 weeks of age

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1983.244.1.e93 ◽

1983 ◽

Vol 244 (1) ◽

pp. E93-E100 ◽

Cited By ~ 10

Author(s):

M. N. Goodman ◽

S. M. Dluz ◽

M. A. McElaney ◽

E. Belur ◽

N. B. Ruderman

Keyword(s):

Skeletal Muscle ◽

Insulin Sensitivity ◽

Glucose Transport ◽

Early Development ◽

Glucose Utilization ◽

Insulin Dose ◽

Insulin Binding ◽

Sprague Dawley ◽

High Insulin ◽

The Right

It has been demonstrated that aging diminishes the rate of glucose utilization by rat skeletal muscle. To determine the basis for this occurrence as well as its temporal sequence, glucose utilization was examined in isolated hindquarters of 3-, 5-, 8-, 16-, 24-, 48-, and 96-wk-old male Sprague-Dawley rats. Glucose utilization diminished progressively during early development (3-5 wk) and adolescence (5-16 wk) in hindquarters perfused in the absence of added insulin. At the same time there was a progressive shift of the insulin dose-response curve to the right, indicating diminished insulin sensitivity and a marked decrease in maximum insulin responsiveness. In contrast, between 24 and 96 wk of age, insulin sensitivity and the rate of glucose utilization in the absence of added insulin did not decrease, and there was only a small decrease in maximum responsiveness. The rate-limiting step in glucose utilization under all conditions was glucose transport. Even at high insulin concentrations, free glucose was not detected in the muscle cells of young or old rats, the uptake of 2-deoxyglucose diminished in parallel with that of glucose, and there was no evidence of a defect in glucose metabolism. These findings indicate that in the Sprague-Dawley rat glucose transport into skeletal muscle and in particular its sensitivity and responsiveness to insulin diminish progressively during early development and adolescence. No further marked changes occurred up to at least 96 wk of age. To what extent these early age-associated changes are due to insulin binding and to what extent to alterations in the glucose transport system per se remains to be determined.

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Exercise increases susceptibility of muscle glucose transport to activation by various stimuli

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1990.258.2.e390 ◽

1990 ◽

Vol 258 (2) ◽

pp. E390-E393 ◽

Cited By ~ 33

Author(s):

G. D. Cartee ◽

J. O. Holloszy

Keyword(s):

Insulin Sensitivity ◽

Glucose Transport ◽

Sugar Transport ◽

Insulin Binding ◽

Insulin Mimetic ◽

Increased Sensitivity ◽

Muscle Glucose Transport ◽

Glucose Analogue ◽

Stimulation Of

The insulin sensitivity of glucose transport in skeletal muscle is enhanced after exercise. In this study, stimulation of transport of the nonmetabolizable glucose analogue 3-O-methylglucose by the insulin-mimetic agents vanadate and H2O2 was markedly enhanced in rat epitrochlearis muscles 18 h after a bout of swimming. This increase in susceptibility of the glucose transport process in muscle to stimulation by insulin-mimetic agents that act beyond the insulin-binding step provides evidence that the increased insulin sensitivity results from an effect of exercise on a later step in the activation of glucose transport. Hypoxia and insulin appear to stimulate glucose transport by different pathways in muscle as evidenced by an additivity of their maximal effects. The effect of a submaximal hypoxic stimulus on muscle sugar transport was greatly amplified 3 h after exercise. This increase in susceptibility of glucose transport to stimulation by hypoxia after exercise suggests that the increased sensitivity is not limited to the insulin sensitive pathway. In contrast to exercise (i.e., swimming), in vitro muscle contractions did not result in an increase in sensitivity of muscle glucose transport to insulin, raising the possibility that a humoral factor is necessary for this effect.

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