Covalent phosphorylation in the regulation of glycogen synthase activity

Roach, Peter J.; Larner, Joseph

doi:10.1007/bf01734108

Cited by 90 publications

(39 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Since the rate of glucose oxidation does not exceed 4 to 6 mg/kg ffm * min when measured in the presence ofhigh glucose and insulin concentrations (46), it is conceivable that the glucose-induced increase in insulin-dependent glucose disposal was mostly due to an increase in nonoxidative glucose disposal. In the rat, increasing glucose disposal by the massaction effect of glucose leads to increased glycogen formation despite unaltered fractional activity of glycogen synthase (47,48). The increase in glycogen formation by glucose mass-action could be mediated via an increase in UDP-glucose concentration (47) or an increase in the affinity of the glycogen synthase I-or D-form for UDP-glucose by glucose-6-phosphate (48).…”

Section: Discussionmentioning

confidence: 99%

“…In the rat, increasing glucose disposal by the massaction effect of glucose leads to increased glycogen formation despite unaltered fractional activity of glycogen synthase (47,48). The increase in glycogen formation by glucose mass-action could be mediated via an increase in UDP-glucose concentration (47) or an increase in the affinity of the glycogen synthase I-or D-form for UDP-glucose by glucose-6-phosphate (48). In man, the expected increase in total muscle glycogen content even during maximal glucose and insulin stimulation is within the coefficient ofvariation for measurement of muscle glycogen content from biopsy samples (-10-20%).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Regulation of glycogen synthase and phosphorylase activities by glucose and insulin in human skeletal muscle.

Yki‐Järvinen¹,

Mott²,

Young³

et al. 1987

J. Clin. Invest.

118

View full text Add to dashboard Cite

We examined the insulin dose-response characteristics of human muscle glycogen synthase and phosphorylase activation. We also determined whether increasing the rate of glucose disposal by hyperglycemia at a fixed insulin concentration activates glycogen synthase.Physiological increments in plasma insulin but not glucose increased the fractional activity of glycogen synthase. The ED50: s for insulin stimulation of whole body and forearm glucose disposal were similar and unaffected by glycemia. Glycogen synthase activation was exponentially related to the insulin-mediated component of whole body and forearm glucose disposal at each glucose concentration. Neither insulin nor glucose changed glycogen phosphorylase activity.These results suggest that insulin but not the rate of glucose disposal per se regulates glycogen synthesis by a mechanism that involves dephosphorylation of glycogen synthase but not phosphorylase. This implies that the low glycogen synthase activities found in insulin-resistant states are a consequence of impaired insulin action rather than reduced glucose disposal.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Regulation of glycogen synthase and phosphorylase activities by glucose and insulin in human skeletal muscle.

Yki‐Järvinen¹,

Mott²,

Young³

et al. 1987

J. Clin. Invest.

118

View full text Add to dashboard Cite

show abstract

“…That this may occur is suggested by the observation of Kochan and his colleagues (34,35) that prior exercise diminishes the concentration of glucose-6-phosphate needed to produce a partial activation of glycogen synthase in both human and rat muscle for several hours following exercise. They suggested that, this as well as alterations in the sensitivity of glycogen synthase to other effectors, may be related to the appearance of an intermediate form of the enzyme with a different phosphorylation state (36). Of particular interest was their finding that such alterations in synthase activity (which in general paralleled changes in the AO.5) persisted far longer than the increase in the activity ratio following exercise and that they correlated more closely with the synthesis of muscle glycogen during the period of supercompensation.…”

Section: Discussionmentioning

confidence: 99%

Muscle Glucose Metabolism following Exercise in the Rat

Garetto²,

et al. 1982

View full text Add to dashboard Cite

A B S T R A C T Muscle glycogen stores are depleted during exercise and are rapidly repleted during the recovery period. To investigate the mechanism for this phenomenon, untrained male rats were run for 45 min on a motor-driven treadmill and the ability of their muscles to utilize glucose was then assessed during perfusion of their isolated hindquarters. Glucose utilization by the hindquarter was the same in exercised and control rats perfused in the absence of added insulin; however, when insulin (30-40,000 MU/ml) was added to the perfusate, glucose utilization was greater after exercise. Prior exercise lowered both, the concentration of insulin that half-maximally stimulated glucose utilization (exercise, 150 ,U/ml; control, 480 ,gU/ml) and modestly increased its maximum effect.The increase in insulin sensitivity persisted for 4 h following exercise, but was not present after 24 h. The rate-limiting step in glucose utilization enhanced by prior exercise appeared to be glucose transport across the cell membrane, as in neither control nor exercised rats did free glucose accumulate in the muscle cell.Following exercise, the ability of insulin to stimulate the release of lactate into the perfusate was unaltered; however its ability to stimulate the incorporation of ['4C]glucose into glycogen in certain muscles was enhanced. Thus at a concentration of 75 AU/ml insulin stimulated glycogen synthesis eightfold more in the fast-twitch red fibers of the red gastrocnemius than it did in the same muscle of nonexercised rats. In contrast, insulin only minimally increased glycogen synthesis in the fast-twitch white fibers of the gastrocnemius, which were not glycogen-depleted. The uptake of 2-deoxyglucose by these muscles followed a similar pattern suggesting that glucose transport was also differentially enhanced. Prior exercise did not enhance

show abstract

“…GS activity was determined at a physiologic concentration of substrate (0.3 mM UDPglucose), calculated as nanomoles of UDP-glucose incorporated into glycogen per minute per milligram of total protein, and expressed as fractional velocity (activity assayed at 0.1 mM glucose-6-phosphate divided by the activity at 10 mM glucose-6-phosphate). This is an indicator of the change in the phosphorylation state of GS in response to insulin (47).…”

Section: Methodsmentioning

confidence: 99%