Inhibitor-1 is not required for the activation of glycogen synthase by insulin in skeletal muscle.
Glycogen synthase is an excellent in vitro substrate for protein phosphatase-1 (PP1), which is potently inhibited by the phosphorylated forms of DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, M(r) = 32,000) and Inhibitor-1. To test the hypothesis that the activation of glycogen synthase by insulin is due to a decrease in the inhibition of PP1 by the phosphatase inhibitors, we have investigated the effects of insulin on glycogen synthesis in skeletal muscles from wild-type mice and mice lacking Inhibitor-1 and DARPP-32 as a result of targeted disruption of the genes encoding the two proteins. Insulin increased glycogen synthase activity and the synthesis of glycogen to the same extent in wild-type and knockout mice, indicating that neither Inhibitor-1 nor DARPP-32 is required for the full stimulatory effects of insulin on glycogen synthase and glycogen synthesis in skeletal muscle.
Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
A G
AG
Scrimgeour
P B
PB
Allen
A A
AA
Fienberg
P
P
Greengard
J C
JC
Lawrence
D000818:Animals; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010750:Phosphoproteins; D011506:Proteins / Q000378:metabolism*
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D011506:Proteins; C033035:deinhibitor protein, Canis familiaris; D006006:Glycogen Synthase