How does insulin stimulate glycogen synthesis?
One of the important effects of insulin on intracellular metabolism is its ability to stimulate the synthesis of glycogen in muscle and liver. It does this by promoting a net decrease in the extent of phosphorylation of glycogen synthase, the rate-limiting enzyme in the pathway of glycogen synthesis, which increases its activity. Several years ago glycogen synthase was shown to be phosphorylated and inactivated by cyclic AMP-dependent protein kinase in vitro, suggesting that the effect of insulin on glycogen synthesis, and perhaps other intracellular processes, might be explainable in terms of the ability of the hormone to decrease the concentration of tissue cyclic AMP. However, the subsequent failure to detect a decrease in cyclic AMP concentration in muscle under conditions where glycogen synthase activity was stimulated by insulin, coupled with the discovery of a second glycogen synthase kinase whose activity is unaffected by cyclic nucleotides, now suggests the possibility that insulin may regulate the activity of a different class of protein kinase, through its own "second messenger". The identification and characterization of glycogen synthase kinase-2 and recent information about the regulation of glycogen synthase by phosphorylation-dephosphorylation in vitro and in vivo are presented.
D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D004837:Epinephrine / Q000502:physiology; D006003:Glycogen / Q000096:biosynthesis*; D006006:Glycogen Synthase / Q000378:metabolism; D006007:Glycogen-Synthase-D Phosphatase / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D008112:Liver Glycogen / Q000096:biosynthesis; D051379:Mice; D009132:Muscles / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D008112:Liver Glycogen; D006003:Glycogen; D000242:Cyclic AMP; D006006:Glycogen Synthase; D011494:Protein Kinases; D011972:Receptor, Insulin; D006007:Glycogen-Synthase-D Phosphatase; D004837:Epinephrine