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Decrease in protein tyrosine phosphatase activities in vanadate-treated obese Zucker (fa/fa) rat liver

  • Part II: Biochemical and Physiological Studies
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Abstract

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 thein 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.

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Authors and Affiliations

  1. Department of Biochemistry, University of Saskatchewan, 107 Wiggins Road, S7N 5E5, Saskatoon, Saskatchewan, Canada

    Subbiah Pugazhenthi, Feridoon Tanha, Bruce Dahl & Ramji L. Khandelwal

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  1. Subbiah Pugazhenthi
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  2. Feridoon Tanha
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  3. Bruce Dahl
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  4. Ramji L. Khandelwal
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Pugazhenthi, S., Tanha, F., Dahl, B. et al. Decrease in protein tyrosine phosphatase activities in vanadate-treated obese Zucker (fa/fa) rat liver. Mol Cell Biochem 153, 125–129 (1995). https://doi.org/10.1007/BF01075927

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