title: Gastric inhibitory polypeptide modulates adiposity and fat oxidation under diminished insulin action.
abstract: Gut hormone gastric inhibitory polypeptide (GIP) stimulates insulin secretion from pancreatic beta-cells upon ingestion of nutrients. Inhibition of GIP signaling prevents the onset of obesity and consequent insulin resistance induced by high-fat diet. In this study, we investigated the role of GIP in accumulation of triglycerides into adipocytes and in fat oxidation peripherally using insulin receptor substrate (IRS)-1-deficient mice and revealed that IRS-1(-/-)GIPR(-/-) mice exhibited both reduced adiposity and ameliorated insulin resistance. Furthermore, increased gene expression of CD36 and UCP2 in liver, and increased expression and enzyme activity of 3-hydroxyacyl-CoA dehydrogenase in skeletal muscle of IRS-1(-/-)GIPR(-/-) mice might contribute to the lower respiratory quotient and the higher fat oxidation in light phase. These results suggest that GIP plays a crucial role in switching from fat oxidation to fat accumulation under the diminished insulin action as a potential target for secondary prevention of insulin resistance.
authors.affiliation: Department of Diabetes and Clinical Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Heying
authors.initials: H
authors.lastname: Zhou
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yamada
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tsukiyama
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Miyawaki
authors.forename: Masaya
authors.initials: M
authors.lastname: Hosokawa
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nagashima
authors.forename: Kentaro
authors.initials: K
authors.lastname: Toyoda
authors.forename: Rei
authors.initials: R
authors.lastname: Naitoh
authors.forename: Wataru
authors.initials: W
authors.lastname: Mizunoya
authors.forename: Tohru
authors.initials: T
authors.lastname: Fushiki
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Seino
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004734:Energy Metabolism; D005223:Fats / Q000378:metabolism*; D005749:Gastric Inhibitory Polypeptide / Q000502:physiology*; D007328:Insulin / Q000502:physiology*; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism; D010084:Oxidation-Reduction; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction
chemical_list: D017931:DNA Primers; D005223:Fats; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010750:Phosphoproteins; D005749:Gastric Inhibitory Polypeptide