+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Gpr40 is expressed in enteroendocrine cells and mediates free fatty acid stimulation of incretin secretion

Gpr40 is expressed in enteroendocrine cells and mediates free fatty acid stimulation of incretin secretion

Diabetes 57(9): 2280-2287

The G-protein-coupled receptor Gpr40 is expressed in beta-cells where it contributes to free fatty acid (FFA) enhancement of glucose-stimulated insulin secretion. However, other sites of Gpr40 expression, including the intestine, have been suggested. The transcription factor IPF1/PDX1 was recently shown to bind to an enhancer element within the 5'-flanking region of Gpr40, implying that IPF1/PDX1 might regulate Gpr40 expression. Here, we addressed whether 1) Gpr40 is expressed in the intestine and 2) Ipf1/Pdx1 function is required for Gpr40 expression. In the present study, Gpr40 expression was monitored by X-gal staining using Gpr40 reporter mice and by in situ hybridization. Ipf1/Pdx1-null and beta-cell specific mutants were used to investigate whether Ipf1/Pdx1 controls Gpr40 expression. Plasma insulin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucose levels in response to acute oral fat diet were determined in Gpr40 mutant and control mice. Here, we show that Gpr40 is expressed in endocrine cells of the gastrointestinal tract, including cells expressing the incretin hormones GLP-1 and GIP, and that Gpr40 mediates FFA-stimulated incretin secretion. We also show that Ipf1/Pdx1 is required for expression of Gpr40 in beta-cells and endocrine cells of the anterior gastrointestinal tract. Together, our data provide evidence that Gpr40 modulates FFA-stimulated insulin secretion from beta-cells not only directly but also indirectly via regulation of incretin secretion. Moreover, our data suggest a conserved role for Ipf1/Pdx1 and Gpr40 in FFA-mediated secretion of hormones that regulate glucose and overall energy homeostasis.

(PDF emailed within 0-6 h: $19.90)

Accession: 053436796

Download citation: RISBibTeXText

PMID: 18519800

DOI: 10.2337/db08-0307

Related references

Novel Mechanism of Fatty Acid Sensing in Enteroendocrine Cells: Specific Structures in Oxo-Fatty Acids Produced by Gut Bacteria Are Responsible for CCK Secretion in STC-1 Cells via GPR40. Molecular Nutrition and Food Research 62(19): E1800146, 2018

Free fatty acid receptor GPR120 is highly expressed in enteroendocrine K cells of the upper small intestine and has a critical role in GIP secretion after fat ingestion. Endocrinology 156(3): 837-846, 2015

GPR40, a free fatty acid receptor on pancreatic beta cells, regulates insulin secretion. Hepatology Research 33(2): 171-173, 2005

PPAR-γ activation increases insulin secretion through the up-regulation of the free fatty acid receptor GPR40 in pancreatic β-cells. Plos One 8(1): E50128, 2013

Free fatty acid receptor 1 (FFA(1)R/GPR40) and its involvement in fatty-acid-stimulated insulin secretion. Cell and Tissue Research 322(2): 207-215, 2005

The G-protein-coupled receptor GPR40 directly mediates long-chain fatty acid-induced secretion of cholecystokinin. Gastroenterology 140(3): 903-912, 2011

GPR40 is necessary but not sufficient for fatty acid stimulation of insulin secretion in vivo. Diabetes 56(4): 1087-1094, 2007

Free fatty acid receptor GPR120 and GPR40 are essential for oil-induced GIP secretion. Journal of Diabetes Investigation 2019, 2019

Free fatty acids increase cytosolic free calcium and stimulate insulin secretion from beta-cells through activation of GPR40. Molecular and Cellular Endocrinology 263(1-2): 173-180, 2006

Free fatty acids regulate insulin secretion from pancreatic b cells through GPR40. Nature 422: 3-6, 2003

Reevaluation of Fatty acid receptor 1 FFAR1/GPR40 as drug target for the stimulation of insulin secretion in humans. 2013

Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40. Nature 422(6928): 173-176, 2003

Short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine cells and mucosal mast cells in rat intestine. Cell and Tissue Research 324(3): 353-360, 2006

Bacterial metabolite indole modulates incretin secretion from intestinal enteroendocrine L cells. Cell Reports 9(4): 1202-1208, 2015

Free Fatty Acid Receptors in Enteroendocrine Cells. Endocrinology 159(7): 2826-2835, 2018