Inhibition of pyruvate oxidation in rat islets by alpha-cyano-4-hydroxycinnamate. Differential effects on insulin secretion and inositol lipid metabolism.

The oxidation of 14C-pyruvate by isolated rat pancreatic islets was inhibited competitively and in a concentration-dependent manner by alpha-cyano-4-hydroxycinnamate. A similar, though less marked inhibition was observed of U-14C-glucose oxidation, although oxidation of 1-14C-glucose was slightly enhanced in the presence of the drug. The rate of glycolysis, as estimated by the utilisation of 5-[3H]-glucose and levels of ATP in islets were unaffected by alpha-cyano-4-hydroxycinnamate. The inhibition of pyruvate oxidation by alpha-cyano-4-hydroxycinnamate was accompanied by an inhibition of insulin secretion in response to glucose, but not to a combination of Ba2+ and theophylline. In contrast, glucose-stimulated inositol lipid breakdown was not affected by the drug. Thus, mitochondrial oxidation of pyruvate appears to be a prerequisite for glucose-stimulated insulin secretion, but not enhanced inositol lipid metabolism.