Antidiabetic action of vanadyl in rats independent of in vivo insulin-receptor kinase activity.
The effects of oral vanadyl sulfate administration for 9-12 days on carbohydrate and lipid metabolism in the basal state and on glucose dynamics during submaximal hyperinsulinemic clamps were investigated in nondiabetic and streptozocin-induced diabetic rats. Decreases in growth rate and water and food consumption were the only significant alterations noted in control animals receiving vanadyl. Administration of vanadyl to diabetic rats resulted in weight loss; a significant decrease in plasma glucose, triglyceride, and cholesterol levels; and decreases in food and water intake, without a concomitant change in plasma insulin concentrations. Vanadyl treatment did not modify either peripheral glucose utilization or hepatic glucose production in control rats during submaximal insulin clamps. In contrast, vanadyl therapy increased insulin-induced glucose utilization significantly and had a small but nonsignificant effect on insulin-mediated suppression of glucose production in diabetic rats. The tyrosine kinase activity of liver- and muscle-derived insulin receptors from diabetic rats that underwent clamp study, which reflected the in vivo phosphorylation state of insulin receptor, was not altered by vanadyl treatment. In conclusion, these results show that augmentation of peripheral glucose utilization is the major determinant of the antidiabetic action of vanadyl and support the notion that the action of vanadyl is independent of insulin-receptor kinase activity.
Venkatesan
N
N
Department of Medicine, Cedars-Sinai Medical Center, University of California, Los Angeles 90048.
Avidan
A
A
Davidson
M B
MB
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism*; D007004:Hypoglycemic Agents; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D012016:Reference Values; D014638:Vanadates / Q000494:pharmacology*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D014638:Vanadates; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin