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タイトル: | Chronic Reduction of GIP Secretion Alleviates Obesity and Insulin Resistance Under High-Fat Diet Conditions. |
著者: | Nasteska, Daniela Harada, Norio Suzuki, Kazuyo https://orcid.org/0000-0001-5716-5242 (unconfirmed) Yamane, Shunsuke Hamasaki, Akihiro Joo, Erina Iwasaki, Kanako Shibue, Kimitaka Harada, Takanari Inagaki, Nobuya |
著者名の別形: | 原田, 範雄 稲垣, 暢也 |
発行日: | Jul-2014 |
出版者: | American Diabetes Association |
誌名: | Diabetes |
巻: | 63 |
号: | 7 |
開始ページ: | 2332 |
終了ページ: | 2343 |
抄録: | Gastric inhibitory polypeptide (GIP) exhibits potent insulinotropic effects on β-cells and anabolic effects on bone formation and fat accumulation. We explored the impact of reduced GIP levels in vivo on glucose homeostasis, bone formation, and fat accumulation in a novel GIP-GFP knock-in (KI) mouse. We generated GIP-GFP KI mice with a truncated prepro-GIP gene. The phenotype was assessed in heterozygous and homozygous states in mice on a control fat diet and a high-fat diet (HFD) in vivo and in vitro. Heterozygous GIP-GFP KI mice (GIP-reduced mice [GIP(gfp/+)]) exhibited reduced GIP secretion; in the homozygous state (GIP-lacking mice [GIP(gfp/gfp)]), GIP secretion was undetectable. When fed standard chow, GIP(gfp/+) and GIP(gfp/gfp) mice showed mild glucose intolerance with decreased insulin levels; bone volume was decreased in GIP(gfp/gfp) mice and preserved in GIP(gfp/+) mice. Under an HFD, glucose levels during an oral glucose tolerance test were similar in wild-type, GIP(gfp/+), and GIP(gfp/gfp) mice, while insulin secretion remained lower. GIP(gfp/+) and GIP(gfp/gfp) mice showed reduced obesity and reduced insulin resistance, accompanied by higher fat oxidation and energy expenditure. GIP-reduced mice demonstrate that partial reduction of GIP does not extensively alter glucose tolerance, but it alleviates obesity and lessens the degree of insulin resistance under HFD conditions, suggesting a potential therapeutic value. |
著作権等: | © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
URI: | http://hdl.handle.net/2433/189090 |
DOI(出版社版): | 10.2337/db13-1563 |
PubMed ID: | 24584548 |
出現コレクション: | 学術雑誌掲載論文等 |
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