Tissue-specific expression and regulation of GSK-3 in human skeletal muscle and adipose tissue

2006 ◽  
Vol 291 (5) ◽  
pp. E891-E898 ◽  
Author(s):  
Theodore P. Ciaraldi ◽  
Deborah K. Oh ◽  
Louis Christiansen ◽  
Svetlana E. Nikoulina ◽  
Alice P. S. Kong ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Protein Expression ◽  
Insulin Action ◽  
Glycogen Synthase ◽  
Serine Phosphorylation ◽  
Whole Body ◽  
Glucose Disposal ◽  
Specific Expression ◽  
Gsk 3Β

Glycogen synthase kinase-3 (GSK-3) is a ubiquitous kinase implicated in both insulin action and adipogenesis. To determine how these multiple roles may relate to insulin resistance, we studied the regulation of GSK-3 protein expression and phosphorylation in skeletal muscle and isolated adipocytes from nonobese healthy control (HC), obese control (OC), and obese type 2 diabetic (OT2D) subjects. At baseline there were no differences in the GSK-3 protein expression in adipocytes. OC subjects underwent a 6-mo caloric restriction resulting in a 7% decrease in body mass index (BMI) and a 21% improvement in insulin-stimulated whole body glucose disposal rate (GDR). GSK-3α and GSK-3β expression decreased in adipocytes ( P < 0.05), whereas GSK-3α protein expression increased in skeletal muscle ( P < 0.05). OT2D subjects were treated with troglitazone or metformin for 3–4 mo. After troglitazone treatment GDR improved ( P < 0.05) despite an increase in BMI ( P < 0.05), whereas metformin had no significant effect on GDR. There was no significant change in GSK-3 expression in adipocytes following troglitazone, whereas both GSK-3α and -β were decreased in skeletal muscle ( P < 0.05). Metformin treatment had no significant impact on GSK-3 protein expression in either adipocytes or skeletal muscle. Neither treatment influenced GSK-3 serine phosphorylation in skeletal muscle or adipocytes. These results suggest that there is tissue specificity for the regulation of GSK-3 in humans. In skeletal muscle GSK-3 plays a role in control of metabolism and insulin action, whereas the function in adipose tissue is less clear.

Acute selective glycogen synthase kinase-3 inhibition enhances insulin signaling in prediabetic insulin-resistant rat skeletal muscle

2005 ◽  
Vol 288 (6) ◽  
pp. E1188-E1194 ◽  
Author(s):  
Betsy B. Dokken ◽  
Julie A. Sloniger ◽  
Erik J. Henriksen
Keyword(s):  
Skeletal Muscle ◽  
Tyrosine Phosphorylation ◽  
Glucose Transport ◽  
Insulin Signaling ◽  
Insulin Action ◽  
Glycogen Synthase ◽  
Serine Phosphorylation ◽  
Zucker Rats ◽  
Type I ◽  
Insulin Resistant

Glycogen synthase kinase-3 (GSK3) has been implicated in the multifactorial etiology of skeletal muscle insulin resistance in animal models and in human type 2 diabetic subjects. However, the potential molecular mechanisms involved are not yet fully understood. Therefore, we determined if selective GSK3 inhibition in vitro leads to an improvement in insulin action on glucose transport activity in isolated skeletal muscle of insulin-resistant, prediabetic obese Zucker rats and if these effects of GSK3 inhibition are associated with enhanced insulin signaling. Type I soleus and type IIb epitrochlearis muscles from female obese Zucker rats were incubated in the absence or presence of a selective, small organic GSK3 inhibitor (1 μM CT118637, Ki < 10 nM for GSK3α and GSK3β). Maximal insulin stimulation (5 mU/ml) of glucose transport activity, glycogen synthase activity, and selected insulin-signaling factors [tyrosine phosphorylation of insulin receptor (IR) and IRS-1, IRS-1 associated with p85 subunit of phosphatidylinositol 3-kinase, and serine phosphorylation of Akt and GSK3] were assessed. GSK3 inhibition enhanced ( P <0.05) basal glycogen synthase activity and insulin-stimulated glucose transport in obese epitrochlearis (81 and 24%) and soleus (108 and 20%) muscles. GSK3 inhibition did not modify insulin-stimulated tyrosine phosphorylation of IR β-subunit in either muscle type. However, in obese soleus, GSK3 inhibition enhanced (all P < 0.05) insulin-stimulated IRS-1 tyrosine phosphorylation (45%), IRS-1-associated p85 (72%), Akt1/2 serine phosphorylation (30%), and GSK3β serine phosphorylation (39%). Substantially smaller GSK3 inhibitor-mediated enhancements of insulin action on these insulin signaling factors were observed in obese epitrochlearis. These results indicate that selective GSK3 inhibition enhances insulin action in insulin-resistant skeletal muscle of the prediabetic obese Zucker rat, at least in part by relieving the deleterious effects of GSK3 action on post-IR insulin signaling. These effects of GSK3 inhibition on insulin action are greater in type I muscle than in type IIb muscle from these insulin-resistant animals.

Fasting inhibits insulin-mediated glycolysis and anaplerosis in human skeletal muscle

1991 ◽  
Vol 261 (5) ◽  
pp. E598-E605 ◽  
Author(s):  
C. E. Castillo ◽  
A. Katz ◽  
M. K. Spencer ◽  
Z. Yan ◽  
B. L. Nyomba
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Glycogen Synthase ◽  
Fat Free Mass ◽  
Whole Body ◽  
Glucose Disposal ◽  
Glycolytic Flux ◽  
Quadriceps Femoris Muscle ◽  
Before And After ◽  
Femoris Muscle

uglycemic (approximately 5.5 mM) hyperinsulinemic (60 mU.m-2.min-1) clamps were performed for 2 h after a 10-h fast and after a prolonged (72-h) fast. Biopsies were obtained from the quadriceps femoris muscle before and after each clamp. The rate of whole body glucose disposal was approximately 50% lower during the clamp after the 72-h fast (P less than or equal to 0.001). The increase in carbohydrate (CHO) oxidation (which is proportional to glycolysis) during the clamp after the 10-h fast (to 13.8 +/- 1.5 mumol.kg fat free mass-1.min-1) was completely abolished during the clamp after the 72-h fast (1.7 +/- 0.6; P less than or equal to 0.001). During the clamp after the 10-h fast, postphosphofructokinase (PFK) intermediates and malate in muscle increased, whereas glutamate decreased (P less than or equal to 0.05-0.001 vs. basal) and citrate did not change. During the clamp after the 72-h fast, there were no significant changes in post-PFK intermediates or glutamate (P greater than 0.05 vs. basal), but there was a decrease in citrate (P less than or equal to 0.01 vs. basal). Euglycemic hyperinsulinemia increased glycogen synthase fractional activity in muscle under both conditions but to a greater extent after the 72-h fast (P less than or equal to 0.01). It is concluded that insulin (after 10-h fast) increases glycolytic flux and the content of malate in muscle, which is probably due to increased anaplerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of increased free fatty acid supply on glucose metabolism and skeletal muscle glycogen synthase activity in normal man

1992 ◽  
Vol 82 (2) ◽  
pp. 219-226 ◽  
Author(s):  
A. B. Johnson ◽  
M. Argyraki ◽  
J. C. Thow ◽  
B. G. Cooper ◽  
G. Fulcher ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Lipid Oxidation ◽  
Muscle Glycogen ◽  
Glucose Oxidation ◽  
Glycogen Synthase ◽  
Whole Body ◽  
Glucose Disposal ◽  
Oxidation Rates ◽  
Glycogen Synthase Activity

1. Experimental elevation of plasma non-esterified fatty acid concentrations has been postulated to decrease insulin-stimulated glucose oxidation and storage rates. Possible mechanisms were examined by measuring skeletal muscle glycogen synthase activity and muscle glycogen content before and during hyperinsulinaemia while fasting plasma non-esterified fatty acid levels were maintained. 2. Fasting plasma non-esterified fatty acid levels were maintained in seven healthy male subjects by infusion of 20% (w/v) Intralipid (1 ml/min) for 120 min before and during a 240 min hyperinsulinaemic euglycaemic clamp (100 m-units h−1 kg−1) combined with indirect calorimetry. On the control day, 0.154 mol/l NaCl was infused. Vastus lateralis muscle biopsy was performed before and at the end of the insulin infusion. 3. On the Intralipid study day serum triacylglycerol (2.24 ± 0.20 versus 0.67 ± 0.10 mmol/l), plasma non-esterified fatty acid (395 ± 13 versus 51 ± 1 μmol/l), blood glycerol (152 ± 2 versus 11 ± 1 μmol/l) and blood 3-hydroxybutyrate clamp levels [mean (95% confidence interval)] [81 (64–104) versus 4 (3–5) μmol/l] were all significantly higher (all P < 0.001) than on the control study day. Lipid oxidation rates were also elevated (1.07 ± 0.07 versus 0.27 ± 0.08 mg min−1 kg−1, P < 0.001). During the clamp with Intralipid infusion, insulin-stimulated whole-body glucose disposal decreased by 28% (from 8.53 ± 0.77 to 6.17 ± 0.71 mg min−1 kg−1, P < 0.005). This was the result of a 48% decrease in glucose oxidation (3.77 ± 0.32 to 1.95 ± 0.21 mg min−1 kg−1, P<0.001), with no significant change in nonoxidative glucose disposal (4.76 ± 0.49 to 4.22 ± 0.57 mg min−1 kg−1, not significant). 4. Basal and insulin-stimulated glycogen synthase activities (13.1 ± 1.9 versus 11.4 ± 2.3% and 30.8 ± 2.3 versus 27.6 ± 4.5%, respectively) were unaffected by the increased plasma non-esterified fatty acid levels. Similarly, basal (36.1 ± 2.7 versus 37.2 ± 1.4 μmol/g) and stimulated (40.0 ± 0.6 versus 37.6 ± 4.4 μmol/g) muscle glycogen levels were unaltered. Insulin-stimulated hexokinase activity was also not affected (0.52 ± 0.08 versus 0.60 ± 0.08 units/g wet weight). 5. Maintenance of plasma non-esterified fatty acid levels at fasting values resulted in an increase in lipid oxidation and was associated with a decrease in insulin-stimulated whole-body glucose uptake and glucose oxidation rates, but no change in non-oxidative glucose disposal. Increased plasma non-esterified fatty acid levels did not appear to have a direct inhibitory effect on glycogen synthase activity or storage of glucose as glycogen at these insulin levels.

Insulin regulates liver glycogen synthase and glycogen phosphorylase activity reciprocally in rhesus monkeys

1997 ◽  
Vol 272 (1) ◽  
pp. E133-E138 ◽  
Author(s):  
H. K. Ortmeyer ◽  
N. L. Bodkin ◽  
B. C. Hansen
Keyword(s):  
Young Adult ◽  
Rhesus Monkeys ◽  
Insulin Action ◽  
Glycogen Phosphorylase ◽  
Activity Ratio ◽  
Glycogen Synthase ◽  
Whole Body ◽  
Glucose Disposal ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Time Points

In skeletal muscle of both humans and monkeys, the effects of in vivo insulin during a euglycemic hyperinsulinemic clamp on the enzymes and substrates of glycogen metabolism have been well established. In liver, such effects of insulin during a clamp have not been previously studied in primates. To examine insulin action at the liver, euglycemic hyperinsulinemic clamps were performed in 10 lean young adult male rhesus monkeys. Liver biopsies were obtained at three time points: basal (fasting), that is, immediately before the onset of the clamp, and during insulin infusion at 130 and 195 min. Glycogen synthase (GS), glycogen phosphorylase (GP), glucose 6-phosphate (G-6-P), and glycogen were determined at each time point, with the greatest effects observed most frequently at 195 min. Whole body insulin-mediated glucose disposal rate was related to the change in the independent activity of GS (r = 0.63, P < 0.05). Insulin increased the GS fractional activity (P < 0.005) and decreased the activity ratio of GP (P < 0.001) compared with basal. The changes in fractional activity of GS and in activity ratio of GP were inversely related (r = - 0.68, P < 0.05), G-6-P concentration was decreased during insulin stimulation compared with basal (P = 0.01). Glycogen concentration was not significantly different between the basal and insulin-stimulated time points. We conclude that insulin during a euglycemic clamp activates liver GS while inhibiting liver GP and that insulin action on liver GS is positively related to whole body insulin-mediated glucose disposal rates in lean young adult rhesus monkeys.

Abstract T P114: Insulin Resistance in Skeletal Muscle of Chronic Stroke

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Alice S Ryan ◽  
Heidi Ortmeyer ◽  
Frederick Ivey ◽  
Charlene Hafer-Macko
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Insulin Action ◽  
Glycogen Synthase ◽  
Chronic Stroke ◽  
Whole Body ◽  
Wide Range

Risk of glucose intolerance and diabetes increases in chronic stroke. The purpose of this study was to assess insulin sensitivity and glycogen synthase (GS), a known benchmark index of insulin action in skeletal muscle, and to compare the activity of this important regulatory enzyme between paretic (P) and non-paretic (NP) skeletal muscle in chronic stroke. We measured insulin sensitivity (M) and bilateral GS fractional activity (ratio of independent to total activity), in lyophilized microdissected muscle samples obtained after an overnight fast and 2 hrs into a 3-hr 80 mU . m -2. min -1 hyperinsulinemic-euglycemic clamp in 21 stroke survivors (n=15 men, n=6 women) (age: 59±2 yrs, BMI: 31±2 kg/m 2 , X±SEM). All had hemiparetic gait after ischemic stroke (>6 months), low aerobic capacity (VO 2 peak, 19.7±1.3 ml/kg/min), and wide range of %body fat (11-48%). Leg lean mass was lower in P than NP (9.3±0.5 vs. 10.0±0.5 kg, P<0.001). Subjects had either normal glucose tolerance (n=7), impaired glucose tolerance (n=7), or diabetes (n=7) and insulin resistance (M: 38.5±2.6 umol/kgFFM/min). Insulin robustly increased GS fractional activity (basal vs. insulin) in P (2.8±0.4 vs.7.5±0.8%, P<0.00001) and NP (2.7±0.4 vs. 9.1±1.1%, P<0.00001) muscle. The %change was greater in NP than P (213±32 vs. 296±36%, P=0.04). The effect of in vivo insulin to increase GS fractional activity was associated with M in P and NP muscle (r=0.59 and r=0.49, P<0.05). In conclusion, muscle atrophy and a reduction in insulin action in paretic muscle likely contribute to whole body insulin resistance in chronic stroke.

scholarly journals Defective Activation of Skeletal Muscle and Adipose Tissue Lipolysis in Type 1 Diabetes Mellitus during Hypoglycemia

2003 ◽  
Vol 88 (4) ◽  
pp. 1503-1511 ◽  
Author(s):  
Staffan Enoksson ◽  
Sonia K. Caprio ◽  
Frances Rife ◽  
Gerald I. Shulman ◽  
William V. Tamborlane ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Skeletal Muscle ◽  
Type 1 Diabetes ◽  
Adipose Tissue ◽  
Type 1 Diabetes Mellitus ◽  
Extracellular Fluid ◽  
Whole Body ◽  
Glucose Disposal ◽  
Plasma Epinephrine

The increased risk of hypoglycemia during intensified treatment of type 1 diabetes mellitus (T1DM) patients, who have a deficient glucagon secretory response, is largely attributed to the development of suppressed adrenomedullary responses. A consequence of this impairment of catecholamine secretion might be reduced lipolysis in major target tissues (muscle and adipose) and, in turn, increased glucose metabolism. To test this hypothesis, we used microdialysis to monitor glycerol (index of lipolysis) in the extracellular fluid of skeletal muscle and adipose tissue and assessed whole-body glucose use by measuring [6,6-2H2]glucose enrichment in plasma in seven intensively treated T1DM patients and eight nondiabetic subjects who received a 3-h insulin infusion (0.8 mU/kg·min) on two occasions: during mild-moderate hypoglycemia or euglycemia. In the hypoglycemic study, the rise in plasma epinephrine was approximately 50% less in the T1DM patients despite a greater fall in plasma glucose (to 3.0 vs. 3.5 mm in controls; P &lt; 0.05). Moreover, the rate of glucose flux and the plasma-extracellular fluid glucose gradient in muscle was increased during hypoglycemia in T1DM subjects compared with controls. Glycerol levels in muscle, adipose, and plasma fell similarly in both groups in the first hour. Thereafter, tissue glycerol remained suppressed in the T1DM patients but rebounded significantly (P &lt; 0.01) in the control subjects. The glycerol response in muscle and adipose tissue was significantly correlated with plasma epinephrine concentration (r = 0.73, P = 0.002; and r = 0.52, P = 0.04, respectively), and inversely correlated with whole-body glucose disposal (r = −0.51, P = 0.05; and r = −0.50, P = 0.05). To determine whether the absence of the lipolytic response is limited to deficient catecholamine release, we perfused muscle and adipose tissue in situ with the selective β2-agonist terbutaline during hyperinsulinemic euglycemia. Local addition of agonist increased glycerol and blood flow in both muscle and adipose (P &lt; 0.01 and P &lt; 0.05, respectively) similarly in T1DM and control subjects. We conclude that deficient release of (rather than impaired responsiveness to) catecholamines in T1DM prevents the local fat breakdown within muscle and adipose tissue that normally occurs during mild-moderate hypoglycemia. This defect within peripheral tissues may lead to a delayed increase in glucose disposal that could contribute to the severity of hypoglycemia when it is prolonged.

scholarly journals Genetic and metabolic effects on skeletal muscle AMPK in young and older twins

2009 ◽  
Vol 297 (4) ◽  
pp. E956-E964 ◽  
Author(s):  
Brynjulf Mortensen ◽  
Pernille Poulsen ◽  
Lise Wegner ◽  
Kirstine L. Stender-Petersen ◽  
Rasmus Ribel-Madsen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
Aerobic Capacity ◽  
Glycogen Synthase ◽  
Metabolic Effects ◽  
Whole Body ◽  
Protein Levels ◽  
Glucose And Lipid Metabolism ◽  
The One ◽  
Expression And Activity

The protein complex AMP-activated protein kinase (AMPK) is believed to play an important role in the regulation of skeletal muscle glucose and lipid metabolism. Defects in the AMPK system might therefore be an important factor in the pathogenesis of type 2 diabetes. We aimed to identify genetic and environmental mechanisms involved in the regulation of AMPK expression and activity and to examine the association between AMPK protein levels and activity on the one hand, and glucose and fat metabolism on the other. We investigated skeletal muscle biopsies from 100 young and 82 older mono- and dizygotic nondiabetic twins excised during the basal and insulin-stimulated states of a physiological hyperinsulinemic-euglycemic clamp. AMPKα1, -α2, and -γ3 mRNA expression was investigated using real-time PCR, and Western blotting was employed to measure protein levels. Multiple regression analyses indicated that skeletal muscle AMPK mRNA and protein expression as well as activity were regulated by sex, age, obesity, and aerobic capacity. Comparison of intraclass correlations on AMPK measurements from mono- and dizygotic twins suggested that skeletal muscle AMPK expression was under minor genetic influence. AMPKγ3 protein expression and activity were negatively related to whole body glucose uptake through the nonoxidative metabolic pathway and positively related to phosphorylation of glycogen synthase. Our results suggest that skeletal muscle AMPK expression is under minor genetic control but regulated by age and sex and associated with obesity and aerobic capacity. Furthermore, our results indicate a role for γ3-containing AMPK complexes in downregulation of insulin-stimulated nonoxidative glucose metabolism possibly through inhibition of glycogen synthase activity.

Unlike insulin, amino acids stimulate p70S6Kbut not GSK-3 or glycogen synthase in human skeletal muscle

2004 ◽  
Vol 286 (4) ◽  
pp. E523-E528 ◽  
Author(s):  
Zhenqi Liu ◽  
Yangsong Wu ◽  
Edward W. Nicklas ◽  
Linda A. Jahn ◽  
Wendie J. Price ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Amino Acid ◽  
Human Skeletal Muscle ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Whole Body ◽  
Glucose Disposal ◽  
Vastus Lateralis Muscle ◽  
Euglycemic Hyperinsulinemic Clamp

Insulin stimulates muscle glucose disposal via both glycolysis and glycogen synthesis. Insulin activates glycogen synthase (GS) in skeletal muscle by phosphorylating PKB (or Akt), which in turn phosphorylates and inactivates glycogen synthase kinase 3 (GSK-3), with subsequent activation of GS. A rapamycin-sensitive pathway, most likely acting via ribosomal 70-kDa protein S6 kinase (p70S6K), has also been implicated in the regulation of GSK-3 and GS by insulin. Amino acids potently stimulate p70S6K, and recent studies on cultured muscle cells suggest that amino acids also inactivate GSK-3 and/or activate GS via activating p70S6K. To assess the physiological relevance of these findings to normal human physiology, we compared the effects of amino acids and insulin on whole body glucose disposal, p70S6K, and GSK-3 phosphorylation, and on the activity of GS in vivo in skeletal muscle of 24 healthy human volunteers. After an overnight fast, subjects received intravenously either a mixed amino acid solution (1.26 μmol·kg-1·min-1× 6 h, n = 9), a physiological dose of insulin (1 mU·kg-1·min-1euglycemic hyperinsulinemic clamp × 2 h, n = 6), or a pharmacological dose of insulin (20 mU·kg-1·min-1euglycemic hyperinsulinemic clamp × 2 h, n = 9). Whole body glucose disposal rates were assessed by calculating the steady-state glucose infusion rates, and vastus lateralis muscle was biopsied before and at the end of the infusion. Both amino acid infusion and physiological hyperinsulinemia enhanced p70S6Kphosphorylation without affecting GSK-3 phosphorylation, but only physiological hyperinsulinemia also increased whole body glucose disposal and GS activity. In contrast, a pharmacological dose of insulin significantly increased whole body glucose disposal, p70S6K, GSK-3 phosphorylation, and GS activity. We conclude that amino acids at physiological concentrations mediate p70S6Kbut, unlike insulin, do not regulate GSK-3 and GS phosphorylation/activity in human skeletal muscle.

Topiramate treatment causes skeletal muscle insulin sensitization and increased Acrp30 secretion in high-fat-fed male Wistar rats

2005 ◽  
Vol 289 (6) ◽  
pp. E1015-E1022 ◽  
Author(s):  
Jason J. Wilkes ◽  
M. T. Audrey Nguyen ◽  
Gautam K. Bandyopadhyay ◽  
Elizabeth Nelson ◽  
Jerrold M. Olefsky
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Drug Treatment ◽  
Wistar Rats ◽  
Whole Body ◽  
Glucose Disposal ◽  
High Fat ◽  
Fourfold Increase ◽  
Male Wistar Rats

We show that Topiramate (TPM) treatment normalizes whole body insulin sensitivity in high-fat diet (HFD)-fed male Wistar rats. Thus drug treatment markedly lowered glucose and insulin levels during glucose tolerance tests and caused increased insulin sensitization in adipose and muscle tissues as assessed by euglycemic clamp studies. The insulin-stimulated glucose disposal rate increased twofold (indicating enhanced muscle insulin sensitivity), and suppression of circulating FFAs increased by 200 to 300%, consistent with increased adipose tissue insulin sensitivity. There were no effects of TPM on hepatic insulin sensitivity in these TPM-treated HFD-fed rats. In addition, TPM administration resulted in a three- to fourfold increase in circulating levels of total and high-molecular-weight (HMW) adiponectin (Acrp30). Western blot analysis revealed normal AMPK (Thr172) phosphorylation in liver with a twofold increased phospho-AMPK in skeletal muscle in TPM-treated rats. In conclusion, 1) TPM treatment prevents overall insulin resistance in HFD male Wistar rats; 2) drug treatment improved insulin sensitivity in skeletal muscle and adipose tissue associated with enhanced AMPK phosphorylation; and 3) the tissue “specific” effects are associated with increased serum levels of adiponectin, particularly the HMW component.

Hyperglycemia induces accumulation of glucose in human skeletal muscle

1991 ◽  
Vol 260 (4) ◽  
pp. R698-R703 ◽  
Author(s):  
A. Katz ◽  
I. Raz ◽  
M. K. Spencer ◽  
R. Rising ◽  
D. M. Mott
Keyword(s):  
Skeletal Muscle ◽  
Steady State ◽  
Specific Activity ◽  
Glycogen Synthase ◽  
Fat Free Mass ◽  
Whole Body ◽  
Glucose Disposal ◽  
Glucose Tolerant ◽  
Femoris Muscle

The effect of hyperglycemia on whole body substrate utilization and the metabolic profile of skeletal muscle has been investigated. Eight glucose-tolerant men were infused with somatostatin (S) for 190 min. During the last 120 min of S infusion, glucose was infused to achieve a steady-state plasma level of 26 mmol/l. Biopsies were obtained from the quadriceps femoris muscle immediately before and 35 and 120 min after induction of hyperglycemia. Steady-state glucose disposal during hyperglycemia averaged (+/- SE) 33.8 +/- 3.2 mumol.kg fat-free mass-1.min-1, and approximately 70% of the glucose disposal was accounted for by skeletal muscle. Intracellular glucose increased from 0.9 +/- 0.2 mmol/kg dry wt during S to 9.5 +/- 2.5 during hyperglycemia (P less than 0.01). It was estimated that approximately 35% of the glucose taken up by muscle during 120 min of hyperglycemia was not phosphorylated. Muscle contents of alpha-D-glucose 1,6-diphosphate, D-glucose 6-phosphate, ATP, ADP, and AMP (both of which are based on the phosphocreatine-to-creatine ratio), which have been shown to inhibit hexokinase in vitro, did not change significantly during hyperglycemia, nor were there any significant changes in any of the other postphosphofructokinase intermediates, D-fructose 2,6-diphosphate, and citrate. Hyperglycemia did not alter the fractional activities of glycogen synthase or phosphorylase, nor total phosphorylase activity. However, hyperglycemia resulted in a 55% increase in glycogen synthase-specific activity (P less than 0.01). It is concluded that hyperglycemia results in a marked increase in muscle glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

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