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., Cocco, L., Berggren, P.-O., Jang, H.-J., Suh, P.-G. Phospholipase Cβ1 potentiates glucose-stimulated insulin secretion.
Phospholipase C-β1 potentiates glucose-stimulated insulin secretion / 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.. - In: FASEB JOURNAL. - ISSN 1530-6860. - STAMPA. - 33:10(2019), pp. 10668-10679. [10.1096/fj.201802732RR]
Phospholipase C-β1 potentiates glucose-stimulated insulin secretion
Cocco L.;
2019
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., Cocco, L., Berggren, P.-O., Jang, H.-J., Suh, P.-G. Phospholipase Cβ1 potentiates glucose-stimulated insulin secretion.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.