INSULIN DECREASES THE GLYCOGEN-SYNTHASE KINASE-3-ALPHA MESSENGER-RNA LEVELS BY ALTERING ITS STABILITY IN STREPTOZOTOCIN-INDUCED DIABETIC RAT-LIVER

The chronic effect of insulin on the expression of the glycogen syntha se kinase in streptozotocin-induced diabetic rat liver is examined. Th e mRNA levels of glycogen kinase-3 alpha were increased (143% of norma l levels) in diabetic livers and these were normalized by insulin supp lementation to the diabetic animals. Neither diabetes nor insulin supp lementation to diabetic rats altered the transcription rate of glycoge n synthase kinase-3 alpha. However, diabetes caused an increase in the half-life of glycogen synthase kinase-3 alpha mRNA from 5 h in normal hepatocytes to 8 h in diabetic ones. Insulin supplementation to the i ncubation medium of diabetic hepatocytes decreased the half-life of gl ycogen synthase kinase-3 alpha mRNA to a level comparable with normal values. This study suggests that the chronic effect of insulin decreas es the levels of glycogen synthase kinase-3 alpha mRNA by altering its stability. (C) 1995 Academic Press, Inc.