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.
Best
L
L
Department of Medicine, University of Manchester, U.K.
Tomlinson
S
S
D000818:Animals; D003373:Coumaric Acids / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D027501:Monocarboxylic Acid Transporters; D010084:Oxidation-Reduction; D011773:Pyruvates / Q000378:metabolism*; D019289:Pyruvic Acid; D051381:Rats; D013403:Sugar Phosphates / Q000378:metabolism*
D003373:Coumaric Acids; D007295:Inositol Phosphates; D007328:Insulin; D027501:Monocarboxylic Acid Transporters; D011773:Pyruvates; D013403:Sugar Phosphates; C007175:alpha-cyano-4-hydroxycinnamate; D019289:Pyruvic Acid; D005947:Glucose