DIVERGENT EFFECTS OF ARACHIDONATE AND OTHER FREE FATTY-ACIDS ON GLUCOSE-STIMULATED INSULIN RELEASE FROM RAT ISLETS

Long term perifusion of isolated rat islets with 1 mM palmitate with 3 gm/dl albumin for 2 to 4 hrs. before an increase in glucose from 3 mM to 17 mM has been shown to suppress the stimulated release of insulin. In these studies, similar concentrations of myristate, stearate, oleate, palmitoleate, linoleate, linolenate, and gamma-linolenate had similar effects. Arachidonate, under similar conditions, enhanced rather than suppressed the release of insulin. This effect occurred at concentrations as low as 10 mu M (lower than that needed for the suppressive effects of palmitate). This was not prevented by ibuprofen and was not associated with alteration of glucose oxidation. In prior work with palmitate, the fatty acid effects may have been due to suppressive effects of fat oxidation on glucose oxidation and signaling, but the arachidonate effects seen here may be due to metabolites or direct ionic effects.