Gastric inhibitory polypeptide modulates adiposity and fat oxidation under diminished insulin action
Gastric inhibitory polypeptide modulates adiposity and fat oxidation under diminished insulin action
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DOI：
10.1016/j.bbrc.2005.07.164
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发表时间：
2005-09-30
影响因子：
3.1
通讯作者：
Seino, Y
中科院分区：
文献类型：
--
作者：
Zhou, HY;Yamada, Y;Seino, Y
胃肠激素胃抑制多肽(GIP)在摄取营养物质时刺激胰岛β细胞分泌胰岛素。抑制GIP信号可以预防高脂饮食引起的肥胖和胰岛素抵抗的发生。在这项研究中，我们利用胰岛素受体底物(IRS)-1缺陷小鼠，研究了GIP在甘油三酯积累到脂肪细胞和外周脂肪氧化中的作用，发现IRS-1(-/-)GIPR(-/-)小鼠表现出减脂和改善胰岛素抵抗。此外，IRS-1(-/-)GIPR(-/-)小鼠肝脏CD36和UCP2基因表达增加，骨骼肌3-羟基酰辅酶A脱氢酶表达和酶活性增加，可能与光期小鼠呼吸商降低和脂肪氧化增加有关。这些结果表明，GIP作为二级预防胰岛素抵抗的潜在靶点，在胰岛素作用减弱的情况下，在从脂肪氧化到脂肪堆积的转换中起着关键作用。(C)2005 Elsevier Inc.保留所有权利。
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. (C) 2005 Elsevier Inc. All rights reserved.