Role of GPR40 in fatty acid action on the beta cell line INS-1E

Hagit Shapiro; Sigal Shachar; Israel Sekler; Michal Hershfinkel; Michael D Walker

doi:10.1016/j.bbrc.2005.07.042

Role of GPR40 in fatty acid action on the beta cell line INS-1E

Biochem Biophys Res Commun. 2005 Sep 16;335(1):97-104. doi: 10.1016/j.bbrc.2005.07.042.

Authors

Hagit Shapiro¹, Sigal Shachar, Israel Sekler, Michal Hershfinkel, Michael D Walker

Affiliation

¹ Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.

PMID: 16081037
DOI: 10.1016/j.bbrc.2005.07.042

Abstract

GPR40 is a G protein-coupled receptor expressed preferentially in beta cells, that has been implicated in mediating free fatty acid-stimulated insulin release. GPR40 RNAi impaired the ability of palmitic acid (PA) to increase both insulin secretion and intracellular calcium ([Ca2+]i). The PA-dependent [Ca2+]i increase was attenuated by inhibitors of Galphaq, PLC, and SERCA. Thus GPR40 activates the Galphaq pathway, leading to release of Ca2+ from the ER. Yet the GPR40-dependent [Ca2+]i rise was dependent on extracellular Ca2+ and elevated glucose, and was blocked by inhibition of L-type calcium channels (LTCC) or opening of the K(ATP) channel; this suggests that GPR40 promotes Ca2+ influx through up-regulation of LTCC pre-activated by glucose and membrane depolarization. Taken together, the data indicate that GPR40 mediates the increase in [Ca2+]i and insulin secretion through the Galphaq-PLC pathway, resulting in release of Ca2+ from the ER and leading to up-regulation of Ca2+ influx via LTCC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Calcium / metabolism
Calcium Channels, L-Type / metabolism
Cell Line
Endoplasmic Reticulum / drug effects
Endoplasmic Reticulum / metabolism
GTP-Binding Protein alpha Subunits, Gq-G11 / antagonists & inhibitors
GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism
Glucose / metabolism
Glucose / pharmacology
Insulin / metabolism
Insulin Secretion
Ion Channel Gating / drug effects
Islets of Langerhans / cytology*
Islets of Langerhans / drug effects
Islets of Langerhans / metabolism*
Palmitic Acid / metabolism*
Palmitic Acid / pharmacology
Potassium Channels / metabolism
RNA Interference
Rats
Receptors, G-Protein-Coupled / genetics
Receptors, G-Protein-Coupled / metabolism*
Type C Phospholipases / antagonists & inhibitors
Type C Phospholipases / metabolism

Substances

Calcium Channels, L-Type
G-protein-coupled receptor 40, rat
Insulin
Potassium Channels
Receptors, G-Protein-Coupled
Palmitic Acid
Type C Phospholipases
GTP-Binding Protein alpha Subunits, Gq-G11
Glucose
Calcium