Role of protein kinase C isoenzymes in fatty acid stimulation of insulin secretion

Although hyperlipidemia is frequently associated with hyperinsulinemia, the stimulation of insulin secretion by fatty acids in the in vitro studies has remained a matter of constant debate, partly because of the uncertainty about a clearly defined mechanism to explain such a direct effect. In this study, we used a pharmacologic approach to test the hypothesis that protein kinase C (PKC) signal-transduction pathway is involved in fatty acid-stimulated insulin secretion. Isolated rat islets were perifused with either palmitate (C,,:,,) or linoleate (C-18:2) in the absence or presence of selective inhibitors of PKC isoenzymes. Our results suggest a role for Ca2+-independent PKC isoenzymes in the signal transduction of fatty acid-stimulated insulin secretion. The data imply that either the nonconventional and/or atypical isoforms of PKC are involved in the stimulation of insulin release induced by fatty acids.