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 exerts insulin-like effects. In this study, we have examined the in vivo effects of vanadate on PTPases in the liver of obese Zucker rats, a genetic animal model for obesity and type II 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 numbers were significantly (p < 0.01) higher in vanadate-treated obese rats 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 substrates, increased in obese rats. In vanadate-treated obese rat livers, the PTPase activities in both subcellular fractions with these substrates decreased significantly (p < 0.001). The decreases in PTPase activities from these groups of rats were further supported by chromatography on a Mono Q column. These data support the view that inhibition of PTPases plays a role in the insulin-mimetic action of vanadate.
Pugazhenthi
S
S
Department of Biochemistry, University of Saskatchewan, Saskatoon, Canada.
Tanha
F
F
Dahl
B
B
Khandelwal
R L
RL
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D014638:Vanadates / Q000008:administration & dosage*
D014638:Vanadates; D017027:Protein Tyrosine Phosphatases