Effects of diabetes, vanadium, and insulin on glycogen synthase activation in Wistar rats.
In vivo effects of insulin and vanadium treatment on glycogen synthase (GS), glycogen synthase kinase-3 (GSK-3) and protein phosphatase-1 (PP1) activity were determined in Wistar rats with streptozotocin (STZ)-induced diabetes. The skeletal muscle was freeze-clamped before or following an insulin injection (5 U/kg i.v.). Diabetes, vanadium, and insulin in vivo treatment did not affect muscle GSK-3beta activity as compared to controls. Following insulin stimulation in 4-week STZ-diabetic rats muscle GS fractional activity (GSFA) was increased 3 fold (p < 0.05), while in 7-week diabetic rats it remained unchanged, suggesting development of insulin resistance in longer term diabetes. Muscle PP1 activity was increased in diabetic rats and returned to normal after vanadium treatment, while muscle GSFA remained unchanged. Therefore, it is possible that PP1 is involved in the regulation of some other cellular events of vanadium (other than regulation of glycogen synthesis). The lack of effect of vanadium treatment in stimulating glycogen synthesis in skeletal muscle suggests the involvement of other metabolic pathways in the observed glucoregulatory effect of vanadium.
Semiz
Sabina
S
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada.
Orvig
Chris
C
McNeill
John H
JH
D000818:Animals; D001786:Blood Glucose; D003920:Diabetes Mellitus / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D006006:Glycogen Synthase / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000201:enzymology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D054645:Protein Phosphatase 1; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014639:Vanadium / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D014639:Vanadium; D006006:Glycogen Synthase; D038362:Glycogen Synthase Kinase 3; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1