IS THERE A LINK BETWEEN IMPAIRED GLUCOSE-METABOLISM AND PROTEIN-KINASE-C ACTIVITY IN THE DIABETIC HEART

The activity of the beta isoform of protein kinase C (PKCbeta) is redu ced in the diabetic heart. Since this isozyme has been implicated in i nsulin action, we tested the hypothesis that PKCbeta contributes to th e development of impaired glucose metabolism by the noninsulin-depende nt diabetic heart. Exposure of the diabetic heart to buffer containing the protein kinase C activator, phorbol myristate acetate, increased PKCbeta activity in the membrane. Associated with the improvement in P KCbeta activity was a biphasic change in glucose metabolism. The initi al phase was characterized by a breakdown in glycogen stores, a stimul ation in glucose oxidation and a decrease in endogenous fatty acid oxi dation. This was followed by a second phase in which the uptake of glu cose was modestly stimulated. Nonetheless, since the phorbol eater did not overcome the diabetes-linked defect in pyruvate dehydrogenase, th e increase in glycolytic flux was not associated with a rise in glucos e oxidation. Consequently, nearly 50% of the triose units were diverte d into lactate and pyruvate production and the generation of ATP from glucose was restricted. Since insulin promotes not only glucose uptake , but also glycogen synthesis and glucose oxidation, the phorbol ester and insulin effects are very different. Thus, the data do not support a role for PKCbeta in the development of glucose metabolic defects in the hearts of noninsulin-dependent diabetic rats.