Budget Amount *help |
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
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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.
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