Phospholipase C-β1 potentiates glucose-stimulated insulin secretion

PLC-beta exerts biologic influences through GPCR. GPCRs are involved in regulating glucose-stimulated insulin secretion (GSIS). Previous studies have suggested that PLC-beta s might play an important role in pancreatic beta cells. However, because of a lack of the specific inhibitors of PLC-beta isozymes and appropriate genetic models, the in vivo function of specific PLC-beta isozymes in pancreatic beta cells and their physiologic relevance in the regulation of insulin secretion have not been studied so far. The present study showed that PLC-beta 1 was crucial for beta-cell function by generation of each PLC-beta conditional knockout mouse. Mice lacking PLC-beta 1 in beta cells exhibited a marked defect in GSIS, leading to glucose intolerance. In ex vivo studies, the secreted insulin level and Ca2+ response in Plcb1(f/f); pancreas/duodenum homeobox protein 1 (Pdx1)-Cre recombinase-estrogen receptor T2 (CreERt2) islets was lower than those in the Plcb1(f/f) islets under the high-glucose condition. PLC-beta 1 led to potentiate insulin secretion via stimulation of particular G(q)-protein-coupled receptors. Plcb1(f/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-beta 1 as an important molecule that regulates beta cell insulin secretion and can be considered a candidate for therapeutic intervention in diabetes mellitus.-Hwang, H.-J., Yang, Y. R., Kim, H. Y., Choi, Y., Park, K.-S., Lee, H., Ma, J. S., Yamamoto, M., Kim, J., Chae, Y. C., Choi, J. H., Cocco, L., Berggren, P.-O., Jang, H.-J., Suh, P.-G. Phospholipase C beta 1 potentiates glucose-stimulated insulin secretion.