Calcium-dependent regulation of glycogen synthase activity in a muscle glycogen particle

We varied rates of glucose transport and glycogen synthase I (GS-I) activity (%GS-I) in isolated rat epitrochlearis muscle to examine the role of each process in determining the rate of glycogen accumulation. %GS-I was maintained at or above the fasting basal range during 3 h of incubation with 36 mM glucose and 60 μU/ml insulin. Lithium (2 mM LiCl) added to insulin increased glucose transport rate and muscle glycogen content compared with insulin alone. The glycogen synthase kinase-3β inhibitor GF-109203x (GF; 10 μM) maintained %GS-I about twofold higher than insulin with or without lithium but did not increase glycogen accumulation. When %GS-I was lowered below the fasting range by prolonged incubation with 36 mM glucose and 2 mU/ml insulin, raising rates of glucose transport with bpV(phen) or of %GS-I with GF produced additive increases in glycogen concentration. Phosphorylase activity was unaffected by GF or bpV(phen). In muscles of fed animals, %GS-I was ∼30% lower than in those of fasted rats, and insulin-stimulated glycogen accumulation did not occur unless %GS-I was raised with GF. We conclude that the rate of glucose transport is rate limiting for glycogen accumulation unless %GS-I is below the fasting range, in which case both glucose transport rate and GS activity can limit glycogen accumulation.

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In Vivo Regulation of Liver and Skeletal Muscle Glycogen Synthase Activity by Glucose and Insulin

Diabetes ◽

10.2337/diab.35.6.662 ◽

1986 ◽

Vol 35 (6) ◽

pp. 662-667 ◽

Cited By ~ 31

Author(s):

Y. T. Kruszynska ◽

P. D. Home ◽

K. G. M. M. Alberti

Keyword(s):

Skeletal Muscle ◽

Muscle Glycogen ◽

Glycogen Synthase ◽

Skeletal Muscle Glycogen ◽

Glycogen Synthase Activity

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Effect of hypercorticism on regulation of skeletal muscle glycogen metabolism by epinephrine

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1992.262.4.e434 ◽

1992 ◽

Vol 262 (4) ◽

pp. E434-E439 ◽

Cited By ~ 2

Author(s):

L. Coderre ◽

A. K. Srivastava ◽

J. L. Chiasson

Keyword(s):

Skeletal Muscle ◽

Muscle Glycogen ◽

Glycogen Content ◽

Activity Ratio ◽

Glycogen Synthase ◽

Glycogen Metabolism ◽

Dexamethasone Treatment ◽

Fed State ◽

Glycogen Concentration ◽

Glycogen Synthase Activity

The effect of hypercorticism on the regulation of glycogen metabolism by epinephrine was examined in skeletal muscles using a hindlimb perfusion technique. Rats were injected with either saline or dexamethasone (0.4 mg.kg-1.day-1) for 14 days and were studied in the fed and fasted (24 h) states under saline or epinephrine (10(-7) M) treatment. In the fed state, dexamethasone administration did not affect basal glycogen concentration but decreased glycogen synthase activity ratio in white and red gastrocnemius muscles. Epinephrine failed to decrease glycogen content despite the expected activation of glycogen phosphorylase in the fed dexamethasone-treated rats. Dexamethasone treatment resulted in a threefold increase in the level of muscle adenosine, a phosphorylase a inhibitor. In control rats, fasting was associated with a decrease in muscle glycogen concentration (P less than 0.01) and with an increase in the glycogen synthase activity ratio. Dexamethasone treatment, however, totally abolished both the decreased muscle glycogen content and glycogen synthase activation observed in fasting controls. In the dexamethasone-treated group, fasting restored the glycogenolytic effect of epinephrine. Interestingly, it was associated with decreased muscle adenosine concentrations. These data indicate that, in the fed state, dexamethasone treatment inhibits skeletal muscle glycogenolysis in response to epinephrine despite phosphorylase activation and glycogen synthase inactivation. It is suggested that this abnormality could be due to the inhibition of phosphorylase a by increased muscle adenosine levels.

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Effect of hypercorticism on regulation of skeletal muscle glycogen metabolism by insulin

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1992.262.4.e427 ◽

1992 ◽

Vol 262 (4) ◽

pp. E427-E433 ◽

Cited By ~ 4

Author(s):

L. Coderre ◽

A. K. Srivastava ◽

J. L. Chiasson

Keyword(s):

Muscle Glycogen ◽

Glycogen Content ◽

Activity Ratio ◽

Glycogen Synthase ◽

Glycogen Synthesis ◽

Glycogen Metabolism ◽

Dexamethasone Treatment ◽

Muscle Glycogen Content ◽

Glycogen Synthase Activity ◽

Muscle Glycogen Concentration

The effects of hypercorticism on the regulation of glycogen metabolism by insulin in skeletal muscles was examined by using the hindlimb perfusion technique. Rats were injected daily with either saline or dexamethasone (0.4 mg.kg-1.day-1) for 14 days and were studied in the fed or fasted (24 h) state under saline or insulin (1 mU/ml) treatment. In fed controls, insulin resulted in glycogen synthase activation and in enhanced glycogen synthesis. In dexamethasone-treated animals, basal muscle glycogen concentration remained normal, but glycogen synthase activity ratio was decreased in white and red gastrocnemius and plantaris muscles. Furthermore, insulin failed to activate glycogen synthase and glycogen synthesis. In the controls, fasting was associated with decreased glycogen concentrations and with increased glycogen synthase activity ratio in all four groups of muscles (P less than 0.01). Dexamethasone treatment, however, completely abolished the decrease in muscle glycogen content as well as the augmented glycogen synthase activity ratio associated with fasting. Insulin infusion stimulated glycogen synthesis in fasted controls but not in dexamethasone-treated rats. These data therefore indicate that dexamethasone treatment inhibits the stimulatory effect of insulin on glycogen synthase activity and on glycogen synthesis. Furthermore, hypercorticism suppresses the decrease in muscle glycogen content associated with fasting.

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

Clinical Science ◽

10.1042/cs0820219 ◽

1992 ◽

Vol 82 (2) ◽

pp. 219-226 ◽

Cited By ~ 51

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.

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