Insulin decreases the glycogen synthase kinase-3 alpha mRNA levels by altering its stability in streptozotocin-induced diabetic rat liver.
The chronic effect of insulin on the expression of the glycogen synthase kinase-3 alpha gene in streptozotocin-induced diabetic rat liver is examined. The mRNA levels of glycogen synthase kinase-3 alpha were increased (143% of normal levels) in diabetic livers and these were normalized by insulin supplementation to the diabetic animals. Neither diabetes nor insulin supplementation to diabetic rats altered the transcription rate of glycogen 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 incubation medium of diabetic hepatocytes decreased the half-life of glycogen synthase kinase-3 alpha mRNA to a level comparable with normal values. This study suggests that the chronic effect of insulin decreases the levels of glycogen synthase kinase-3 alpha mRNA by altering its stability.
Department of Biochemistry, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
P V
PV
Rao
S
S
Pugazhenthi
R L
RL
Khandelwal
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D004355:Drug Stability; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007328:Insulin; D012333:RNA, Messenger; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3