Is there a link between impaired glucose metabolism and protein kinase C activity in the diabetic heart?

Stephen W. Schaffer, Cherry Ballard, Mahmood S Mozaffari

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The activity of the β isoform of protein kinase C (PKC(β)) is reduced in the diabetic heart. Since this isozyme has been implicated in insulin action, we tested the hypothesis that PKC(β) 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(β) activity in the membrane. Associated with the improvement in PKC(β) 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(β) in the development of glucose metabolic defects in the hearts of noninsulin-dependent diabetic rats.

Original languageEnglish (US)
Pages (from-to)219-225
Number of pages7
JournalMolecular and Cellular Biochemistry
Volume176
Issue number1-2
DOIs
StatePublished - Nov 28 1997

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Metabolism
Protein Kinase C
Glucose
Oxidation
Phorbol Esters
Insulin
Pyruvic Acid
Glycogen
Trioses
Defects
Tetradecanoylphorbol Acetate
Medical problems
Isoenzymes
Rats
Lactic Acid
Buffers
Oxidoreductases
Protein Isoforms
Fatty Acids
Adenosine Triphosphate

Keywords

  • Cardiomyopathy
  • Diabetes mellitus
  • Glucose metabolism
  • Protein kinase C

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Is there a link between impaired glucose metabolism and protein kinase C activity in the diabetic heart? / Schaffer, Stephen W.; Ballard, Cherry; Mozaffari, Mahmood S.

In: Molecular and Cellular Biochemistry, Vol. 176, No. 1-2, 28.11.1997, p. 219-225.

Research output: Contribution to journalArticle

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