HEXOSE METABOLISM IN PANCREATIC-ISLETS - EFFECT OF (-)-HYDROXYCITRATE UPON FATTY-ACID SYNTHESIS AND INSULIN RELEASE IN GLUCOSE-STIMULATED ISLETS

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 pancreatic 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 C-14-labelled acetyl residues derived from L-[U-C-14]leucine into islet lipids. A partial inhibition of fatty acid labelling by (H2O)-H-3 as only observed in islets incubated for 120 min in the presence of 5.0 mM (-)-hydroxycitrate and absence of CaCl2. These findings suggest that (-)-hydroxycitrate is not, under the present experimental conditions, a useful tool to abolish fatty acid synthesis in intact pancreatic islets.