Insulin and Exercise Decrease Glycogen Synthase Kinase-3 Activity by Different Mechanisms in Rat Skeletal Muscle*

Glycogen synthase activity is increased in response to insulin and exercise in skeletal muscle. Part of the mechanism by which insulin stimulates glycogen synthesis may involve phosphorylation and activation of Akt, serine phosphorylation and deactivation of glycogen synthase kinase-3 (GSK-3), leading to dephosphorylation and activation of glycogen synthase. To study Akt and GSK-3 regulation in muscle, time course experiments on the effects of insulin injection and treadmill running exercise were performed in hindlimb skeletal muscle from male rats. Both insulin and exercise increased glycogen synthase activity (%I-form) by 2–3-fold over basal. Insulin stimulation significantly increased Akt phosphorylation and activity, whereas exercise had no effect. The time course of the insulin-stimulated increase in Akt was closely matched by GSK-3α Ser21 phosphorylation and a 40–60% decrease in GSK-3α and GSK-3β activity. Exercise also deactivated GSK-3α and β activity by 40–60%. However, in contrast to the effects of insulin, there was no change in Ser21 phosphorylation in response to exercise. Tyrosine dephosphorylation of GSK-3, another putative mechanism for GSK-3 deactivation, did not occur with insulin or exercise. These data suggest the following: 1) GSK-3 is constitutively active and tyrosine phosphorylated under basal conditions in skeletal muscle, 2) both exercise and insulin are effective regulators of GSK-3 activity in vivo, 3) the insulin-induced deactivation of GSK-3 occurs in response to increased Akt activity and GSK-3 serine phosphorylation, and 4) there is an Akt-independent mechanism for deactivation of GSK-3 in skeletal muscle.

• Publication year

  1999

• Venue

  Journal of Biological Chemistry

• Publication date

  1999-08-27

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/jbc.274.35.24896PMID 10455163
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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