Altered regulation of glycogen metabolism by vasopressin and phenylephrine in hepatocytes from insulin-resistant obese (fa/fa) rats. Role of protein kinase C

Abstract

The hormonal control of glycogen synthase and phosphorylase interconversion was investigated in hepatocytes isolated from lean and genetically obese (fa/fa) rats. In cells from obese animals, the inactivation of synthase by 4β-phorbol 12β-myristate 13α-acetate (PMA), phospholipase C, vasopressin and the α1-adrenergic agonist phenylephrine was markedly impaired, and the property of PMA to counteract phosphorylase activation by phenylephrine was attenuated. The maximal response of phosphorylate activation to phenylephrine and vasopressin was attenuated. The maximal response of phosphorylase activation to phenylephrine and vasopressin was increased in obese-rat hepatocytes, but the sensitivity to these hormones was similar to that in lean-rat hepatocytes. These observations indicate that the defect in protein kinase C that we reported previously in heart of insulin-resistant fa/fa rats [Van de Werve, Zaninetti, Lang, Vallotton and Jeanrenaud (1987) Diabetes 36, 310-319] is probably also expressed in liver.