Reduction of GIP secretion alleviates obesity and insulin resistance under high fat diet condition

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461344
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kyoto University
• Principal Investigator: HARADA NORIO 京都大学, 医学(系)研究科(研究院), 助教 (50530169)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: インクレチン / GIP / インスリン分泌 / 耐糖能 / 骨代謝 / 肥満 / インスリン抵抗性

Outline of Final Research Achievements

We generated GIP-deficient mice with reduced and lacking GIP secretion and examine glucose tolerance, bone formation, and high fat diet (HFD)-induced obesity and insulin resistance. During oral glucose tolerance test (OGTT), heterozygous GIP-reduced mice (GIPgfp/+) had significantly decreased GIP levels (~50%) compared to wild-type mice (WT). In homozygous GIP-lacking mice (GIPgfp/gfp), GIP levels were undetectable. Insulin levels during OGTT were significantly lower in GIPgfp/+ and GIPgfp/gfp. Bone volume in GIPgfp/+ was similar to that in WT, while GIPgfp/gfp had decreased bone volume. Body weight gain and total body fat mass after 8 weeks of HFD were decreased in GIPgfp/+ compared to those in WT; GIPgfp/gfp had the lowest body weight and body fat mass. Insulin sensitivity in GIPgfp/+ and GIPgfp/gfp was improved compared to that in WT from data of insulin tolerance test. Thus, chronic reduction of GIP secretion alleviates obesity and insulin resistance under HFD condition.

Free Research Field

代謝学