Gastric inhibitory polypeptide modulates adiposity and fat oxidation under diminished insulin action.
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.
Zhou
Heying
H
Department of Diabetes and Clinical Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Yamada
Yuichiro
Y
Tsukiyama
Katsushi
K
Miyawaki
Kazumasa
K
Hosokawa
Masaya
M
Nagashima
Kazuaki
K
Toyoda
Kentaro
K
Naitoh
Rei
R
Mizunoya
Wataru
W
Fushiki
Tohru
T
Kadowaki
Takashi
T
Seino
Yutaka
Y
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
D017931:DNA Primers; D005223:Fats; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010750:Phosphoproteins; D005749:Gastric Inhibitory Polypeptide