DOES THE INSULIN-MIMETIC ACTION OF VANADATE INVOLVE INSULIN-RECEPTOR KINASE

Effects of vanadate administration on the insulin receptor status in l iver were examined in streptozotocin-induced diabetic rats. Diabetic r ats were characterized by hyperglycemia (4-foId increase), hypoinsulin emia (81% decrease) and a significant (P <0.01) increase in hepatic in sulin receptor numbers. Autophosphorylation of the beta subunit of ins ulin receptor and its tyrosine kinase activity towards the synthetic p eptide (poly glut(4)tyr(1)) decreased by approximately 60% as a result of diabetes. After chronic treatment of these rats with sodium orthov anadate, the plasma glucose levels were normalized to near control val ues with the hypoinsulinemia remaining unaltered. The insulin-stimulat ed phosphorylation of the beta subunit increased significantly (P <0.0 01) in diabetic rats after treatment with vanadate. However, the impro vement in the tyrosine kinase activity was marginal. In vitro, vanadat e prevented the dephosphorylation of the phosphorylated insulin recept or and increased its tyrosine kinase activity in the absence as well a s presence of insulin. The findings of this study further support the view that insulin receptor is one of the sites involved in the insulin -mimetic actions of vanadate. (Mel Cell Biochem 127/128: 211-218,