Hexose metabolism in pancreatic islets. Effect of (−)-hydroxycitrate upon fatty acid synthesis and insulin release in glucose-stimulated islets

Abstract

Anaplerotic reactions leading to the de novo synthesis of fatty acids were recently proposed to participate in the coupling of metabolic to secretory events in the process of glucose-stimulated insulin release. In an attempt to validate such a proposal, the effect of (−)-hydroxycitrate upon fatty acid synthesis and insulin release was investigated in glucose-stimulated rat pacreatic islets. The inhibitor of ATP citrate-lyase, when tested in the 1.0–2.0 mM range, failed to affect glucose-stimulated insulin release, but also failed to inhibit the incorporation of 14C-labelled acetyl residues derived from l-[U- 14C]leucine into islet lipids. A partial inhibition of fatty acids labelling by 3H 2O was only observed in islets incubated for 120 min in the presence of 5.0 mM (−)-hydroxycitrate and absence of CaCl 2. These findings suggest that (−)-hydroxycitrate is not, under the present experimental conditions, a useful tool to abolish fatty acid synthesis in intact pancreatic islets.