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Title: Chronic Reduction of GIP Secretion Alleviates Obesity and Insulin Resistance Under High-Fat Diet Conditions.
Authors: Nasteska, Daniela
Harada, Norio  kyouindb  KAKEN_id
Suzuki, Kazuyo  kyouindb  KAKEN_id  orcid (unconfirmed)
Yamane, Shunsuke  kyouindb  KAKEN_id
Hamasaki, Akihiro
Joo, Erina
Iwasaki, Kanako
Shibue, Kimitaka
Harada, Takanari
Inagaki, Nobuya  kyouindb  KAKEN_id
Author's alias: 原田, 範雄
稲垣, 暢也
Issue Date: Jul-2014
Publisher: American Diabetes Association
Journal title: Diabetes
Volume: 63
Issue: 7
Start page: 2332
End page: 2343
Abstract: 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.
Rights: © 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 for details.
DOI(Published Version): 10.2337/db13-1563
PubMed ID: 24584548
Appears in Collections:Journal Articles

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