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Gastric inhibitory polypeptide (GIP) is an incretin secreted from enteroendocrine K cells in response to meal ingestion. Recently free fatty acid receptor G protein-coupled receptor (GPR) 120 was identified as a lipid sensor involved in glucagon-like peptide-1 secretion. However, Gpr 120 gene expression and its role in K cells remain unclear, partly due to difficulties in separation of K cells from other intestinal epithelial cells. In this study, we purified K cells using GIP-green fluorescent protein (GFP) knock-in mice, in which K cells can be visualized by GFP fluorescence. GFP-positive cells (K cells) were observed in the small intestine but not in the stomach and colon. K cell number and GIP content in K cells were significantly higher in the upper small intestine than those in the lower small intestine. We also examined the expression levels of several free fatty acid receptors in K cells. Among free fatty acid receptors, GPR120 was highly expressed in the K cells of the upper small intestine compared with the lower small intestine. To clarify the role of GPR120 on K cells in vivo, we used GPR120-deficient mice (GPR120(-/-)). GPR120(-/-) exhibited significantly lower GIP secretion (75% reduction, P < .01) after lard oil ingestion compared with that in wild-type mice. Consistently, pharmacological inhibition of GPR120 with grifolic acid methyl ether in wild-type mice significantly attenuated lard oil-induced GIP secretion. In conclusion, GPR120 is expressed abundantly in K cells of the upper small intestine and plays a critical role in lipid-induced GIP secretion.

Original publication

DOI

10.1210/en.2014-1653

Type

Journal article

Journal

Endocrinology

Publication Date

03/2015

Volume

156

Pages

837 - 846

Addresses

Department of Diabetes, Endocrinology and Nutrition (K.Iw., N.H., K.Sa., S.Y., K.Su., A.Ha., D.N., K.Sh., E.J., T.Har., N.I.), Graduate School of Medicine, and Department of Genomic Drug Discovery Science (K.Ii., A.Hi.), Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8507, Japan; and Faculty of Pharmaceutical Sciences (T.Has., Y.A.), Tokushima Bunri University, Tokushima 770-8514, Japan.

Keywords

Intestinal Mucosa, Intestine, Small, Animals, Mice, Transgenic, Mice, Knockout, Mice, Salicylates, Gastric Inhibitory Polypeptide, Dietary Fats, Green Fluorescent Proteins, Receptors, G-Protein-Coupled, RNA, Messenger, Glucose Tolerance Test, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Regulation, Enteroendocrine Cells, Sesterterpenes