Phospholipase C-β1 potentiates glucose-stimulated insulin secretion

Abstract

PLC-β exerts biologic influences through GPCR. GPCRs are involved in regulating glucose-stimulated insulin secretion (GSIS). Previous studies have suggested that PLC-βs might play an important role in pancreatic β cells. However, because of a lack of the specific inhibitors of PLC-β isozymes and appropriate genetic models, the in vivo function of specific PLC-β isozymes in pancreatic β cells and their physiologic relevance in the regulation of insulin secretion have not been studied so far. The present study showed that PLC-β1 was crucial for β-cell function by generation of each PLC-β conditional knockout mouse. Mice lacking PLC-β1 in β cells exhibited a marked defect in GSIS, leading to glucose intolerance. In ex vivo studies, the secreted insulin level and Ca2+ response in Plcb1f/f; pancreas/duodenum homeobox protein 1 (Pdx1)-Cre recombinase–estrogen receptor T2 (CreERt2) islets was lower than those in the Plcb1f/f islets under the high-glucose condition. PLC-β1 led to potentiate insulin secretion via stimulation of particular Gq-protein–coupled receptors. Plcb1f/f; Pdx1-CreERt2 mice fed a high-fat diet developed more severe glucose intolerance because of a defect in insulin secretion. The present study identified PLC-β1 as an important molecule that regulates β cell insulin secretion and can be considered a candidate for therapeutic intervention in diabetes mellitus.