Insulin secretion, inositol phosphate levels, and phospholipase C isozymesin rodent pancreatic islets

During a dynamic perifusion, 20 mmol/L glucose, 20 mmol/L alpha-ketoisocapr oate (KIC) or 20 mmol/L methyl pyruvate (MP) stimulate biphasic insulin sec retory responses from collagenase-isolated rat islets. Peak first-phase ins ulin responses were comparable for all 3 nutrient agonists. The largest sec ond-phase insulin secretory response was evoked by 20 mmol/L glucose (30-fo ld above basal release rates), and this response was more sustained than th at observed with either 20 mmol/L KIC or 20 mmol/L MP. When mouse islets we re perifused under similar conditions, KIC stimulated the largest first-pha se insulin response, while comparable acute insulin secretion rates were ob tained with glucose- or MP-stimulated islets. In contrast to rat islets, th e sustained second phase of insulin secretion from mouse islets was minimal regardless of the nutrient secretagogue used. This anomalous response of m ouse islets as compared with rat islets could not be ascribed to any obviou s difference in the glucose usage rate or insulin content between these 2 s pecies. Glucose, KIC, or MP stimulated significant increases in H-3-inosito l phosphates in rat islets. Significantly smaller increases were measured i n mouse islets. Comparative Western blot analyses showed pronounced species differences in the expression of phospholipase C beta 1 (PLC beta 1), PLC beta 2, PLC beta 3, and PLC delta 1 but not PLC gamma 1 or protein kinase C alpha (PKC alpha) between rat and mouse islets. PLC beta 4 or PLC delta 2 could not be identified in either species. These findings are consistent wi th the concept that the underexpression of the nutrient-activated PLC isozy me may account for the minimal inositol phosphate (IP) and second-phase ins ulin secretory response from mouse islets. Copyright (C) 2000 by W.B. Saund ers Company.