화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.326, No.4, 744-751, 2005
Lysophosphatidylcholine enhances glucose-dependent insulin secretion via an orphan G-protein-coupled receptor
A lysophospholipid series, such as lysophosphatidic acid, lysophosphatidylserine, and lysophosphaticlylcholine (LPC), is a bioactive lipid mediator with diverse physiological and pathological functions. LPC has been reported to induce insulin secretion from pancreatic P-cells, however, the precise mechanism has remained elusive to date. Here we show that an orphan G-protein-coupled receptor GPR119 plays a pivotal role in this event. LPC potently enhances insulin secretion in response to high concentrations of glucose in the perfused rat pancreas via stimulation of adenylate cyclase, and dose-dependently induces intracellular cAMP accumulation and insulin secretion in a mouse pancreatic beta-cell line, NIT-1 cells. The Gs-protein-coupled receptor for LPC was identified as GPR119, which is predominantly expressed in the pancreas. GPR119-specific siRNA significantly blocked LPC-induced insulin secretion from NIT-1 cells. Our findings suggest that GPR119, which is a novel endogenous receptor for LPC, is involved in insulin secretion from P-cells, and is a potential target for anti-diabetic drug development. (C) 2004 Elsevier Inc. All rights reserved.