Dual Effect of Palmitate on Voltage-Gated Calcium Channels and Insulin Secretion in Pancreatic Beta Cells of Rats

Abstract

A variety of signaling molecules modify voltage-gated calcium channels activity in pancreatic beta cells, among them are, free fatty acids (FFA). Acute exposure to FFA increases glucose-stimulated insulin secretion, while chronic exposure increases basal insulin secretion, but decreases glucose-stimulated (Olofsson et al., 2004; Zhou and Grill, 1994). Preliminary studies in our laboratory showed that pre-incubation with 1 mM palmitate during 48-72 hours reduced barium currents in beta cells. In this work, we analyze the effect of different palmitate concentrations on calcium currents and insulin secretion in beta cells of adult male Wistar rats. Electrophysiological recordings were performed using whole-cell voltage clamp technique. Reverse hemolytic plaque assay measured insulin secretion by isolated beta cells. Pre-incubation with 0.25 and 0.5 mM palmitate during 48-72 h increased the high voltage-activated (HVA) calcium current without affecting the LVA current. An acute 5 min pre-incubation with 0.5 mM palmitate also increased HVA current. In contrast, 24 h pre-incubation with 1 mM decreased both, LVA and HVA currents. A similar effect was observed during an acute incubation. Chronic pre-incubation with 0.25, 0.5 and 1 mM palmitate decreased the percentage of insulin secretory cells, immunoplaque area and insulin secretion index in a glucose-stimulated condition (15.6 mM). Chronic pre-incubation with 0.5 and 1 mM palmitate, also decreased the secretion index at basal glucose (5.6 mM). However, acute pre-incubation with 1 mM palmitate increased the immunoplaque area in 5.6 mM glucose. Together these results show that palmitate has a dual effect, depending on time and concentration on the calcium currents and insulin secretion in beta cells. Partially supported by DGAPA PAPIIT-UNAM Grants: IN213114, M Hiriart; IV100116 to A. Frank and M Hiriart, and IN211416 to M Velasco-Torres.