DECREASE IN PROTEIN-TYROSINE-PHOSPHATASE ACTIVITIES IN VANADATE-TREATED OBESE ZUCKER (FA FA) RAT-LIVER/

The inhibitory action of vanadate towards protein tyrosine phosphatase (PTPase) has been considered as a probable mechanism by which it exer ts insulin-like effects. In this study, we have examined the in vivo e ffects of vanadate on PTPases in the liver of obese Zucker rats, a gen etic animal model for obesity and type LI diabetes. These animals were characterized by hyperinsulinemia and mild hyperglycemia. The number of insulin receptors were significantly (p < 0.01) decreased in liver. After chronic administration of vanadate in obese rats, 80% decrease in the plasma levels of insulin was observed. The insulin receptor num bers were significantly (p < 0.01) higher in vanadate-treated obese ra ts as compared to the untreated ones. The hepatic PTPase activities in cytosolic and particulate fractions, with phosphorylated poly glu:tyr (4:1) and the insulin receptor peptide (residues 1142-1153) as substr ates, increased in obese rats. In vanadate-treated obese rat livers, t he PTPase activities in both subcellular fractions with these substrat es decreased significantly (p < 0.001). The decreases in PTPase activi ties from these groups of rats were further supported by chromatograph y on a Mono Q column. These data support the view that inhibition of P TPases plays a role in the insulin-mimetic action of vanadate.