title: Is there a link between impaired glucose metabolism and protein kinase C activity in the diabetic heart?
abstract: The activity of the beta isoform of protein kinase C (PKC beta) is reduced in the diabetic heart. Since this isozyme has been implicated in insulin action, we tested the hypothesis that PKC beta contributes to the development of impaired glucose metabolism by the noninsulin-dependent diabetic heart. Exposure of the diabetic heart to buffer containing the protein kinase C activator, phorbol myristate acetate, increased PKC beta activity in the membrane. Associated with the improvement in PKC beta activity was a biphasic change in glucose metabolism. The initial phase was characterized by a breakdown in glycogen stores, a stimulation in glucose oxidation and a decrease in endogenous fatty acid oxidation. This was followed by a second phase in which the uptake of glucose was modestly stimulated. Nonetheless, since the phorbol ester did not overcome the diabetes-linked defect in pyruvate dehydrogenase, the increase in glycolytic flux was not associated with a rise in glucose oxidation. Consequently, nearly 50% of the triose units were diverted 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 PKC beta in the development of glucose metabolic defects in the hearts of noninsulin-dependent diabetic rats.
authors.affiliation: University of South Alabama, School of Medicine, Department of Pharmacology, Mobile 36688, USA.
authors.forename: S W
authors.initials: SW
authors.lastname: Schaffer
authors.forename: C
authors.initials: C
authors.lastname: Ballard
authors.forename: M S
authors.initials: MS
authors.lastname: Mozaffari
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D009202:Cardiomyopathies / Q000150:complications / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism* / Q000502:physiology; D006003:Glycogen / Q000032:analysis / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D002273:Carcinogens; D006003:Glycogen; D011493:Protein Kinase C; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate