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.—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., Coceo, L., Berggren, P.‐O., Jang, H.‐J., Suh, P.‐G. Phospholipase Cβ1 potentiates glucose‐stimulated insulin secretion. FASEB J. 33, 10668–10679 (2019). www.fasebj.org