title: Mechanisms of fat-induced gastric inhibitory polypeptide/glucose-dependent insulinotropic polypeptide secretion from K cells.
abstract: Gastric inhibitory polypeptide/glucose-dependent insulinotropic polypeptide (GIP) is one of the incretins, which are gastrointestinal hormones released in response to nutrient ingestion and potentiate glucose-stimulated insulin secretion. Single fat ingestion stimulates GIP secretion from enteroendocrine K cells; chronic high-fat diet (HFD) loading enhances GIP secretion and induces obesity in mice in a GIP-dependent manner. However, the mechanisms of GIP secretion from K cells in response to fat ingestion and GIP hypersecretion in HFD-induced obesity are not well understood. We generated GIP-green fluorescent protein knock-in (GIP (gfp/+)) mice, in which K cells are labeled by enhanced GIP-green fluorescent protein. Microarray analysis of isolated K cells from GIP (gfp/+) mice showed that both fatty acid-binding protein 5 and G protein-coupled receptor 120 are highly expressed in K cells. Single oral administration of fat resulted in significant reduction of GIP secretion in both fatty acid-binding protein 5- and G protein-coupled receptor 120-deficient mice, showing that fatty acid-binding protein 5 and G protein-coupled receptor 120 are involved in acute fat-induced GIP secretion. Furthermore, the transcriptional factor, regulatory factor X6 (Rfx6), is highly expressed in K cells. In vitro experiments using the mouse enteroendocrine cell line, STC-1, showed that GIP messenger ribonucleic acid levels are upregulated by Rfx6. Expression levels of Rfx6 messenger ribonucleic acid as well as that of GIP messenger ribonucleic acid were augmented in the K cells of HFD-induced obese mice, in which GIP content in the small intestine is increased compared with that in lean mice fed a control diet. These results suggest that Rfx6 is involved in hypersecretion of GIP in HFD-induced obese conditions by increasing GIP gene expression.
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition Graduate School of Medicine Kyoto University Kyoto Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yamane
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition Graduate School of Medicine Kyoto University Kyoto Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Harada
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition Graduate School of Medicine Kyoto University Kyoto Japan.
authors.forename: Nobuya
authors.initials: N
authors.lastname: Inagaki
mesh_terms: D000818:Animals; D002460:Cell Line; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism*; D019858:Enteroendocrine Cells / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005749:Gastric Inhibitory Polypeptide / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors / Q000378:metabolism
chemical_list: D004041:Dietary Fats; C498007:FFAR4 protein, mouse; C082667:Fabp5 protein, mouse; D050556:Fatty Acid-Binding Proteins; D009363:Neoplasm Proteins; D043562:Receptors, G-Protein-Coupled; D000071701:Regulatory Factor X Transcription Factors; C547963:Rfx6 protein, mouse; D005749:Gastric Inhibitory Polypeptide
keywords: Fatty acid‐binding protein 5; G protein‐coupled receptor 120; Regulatory factor X6