The mechanisms of GIP secretion from enteroendocrine K cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293210
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kyoto University
• Principal Investigator: INAGAKI NOBUYA 京都大学, 医学(系)研究科(研究院), 教授 (30241954)
• Co-Investigator(Kenkyū-buntansha): Norio Harada 京都大学, 医学(系)研究科, 助教 (50530169)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: インクレチン / GIP / Ｋ細胞 / インスリン分泌 / 肥満

Outline of Final Research Achievements

GIP is an incretin secreted from enteroendocrine K cells in response to nutrient ingestion and potentiates glucose-dependent insulin secretion from pancreatic beta-cells. Fat intake strongly stimulates GIP secretion. However, mechanisms of fat-induced GIP secretion had remained unclear, mainly because of inability to isolate K cells from intestinal epithelium. We generated GIP-green fluorescent protein knock-in (GIP-GFP) mice, in which K cells are labeled by enhanced GFP. Microarray analysis of K cells isolated from GIP-GFP mice enabled us to identify genes that are highly expressed in K cells. Among the genes, we clarified that fatty acid-binding protein 5 (FABP5) and free fatty acid receptor GPR120 play critical roles in GIP secretion in response to a single administration of fat. Furthermore, we demonstrated that transcription factors Rfx6 and Pdx1 are involved in production of GIP under High-fat diet feeding by increasing GIP gene expression in K cells.

Free Research Field

代謝学