Study on metabolism in vivo mediated by gut hormone

作为肠道信号传递到胰腺β细胞的激素因子被称为肠促胰岛素，胃抑制多肽（GIP）被确定为肠促胰岛素之一。GIP是一种由42个氨基酸组成的胃肠道肽激素，由十二指肠内分泌k细胞吸收葡萄糖或脂肪后释放，并通过与其特异性受体GIP受体（GIPR）结合发挥作用。我们对GIPR基因靶向突变的小鼠进行了表征，发现IRS-1(-/-)GIPR（-/-）小鼠表现出肥胖减少和胰岛素抵抗改善，这表明在胰岛素作用减弱的情况下，GIP作为胰岛素抵抗二级预防的潜在靶点，在从脂肪氧化到脂肪积累的转变中起着至关重要的作用。此外，骨组织形态学分析显示，骨形成参数显著降低，破骨细胞数量显著增加，表明GIP受体（-/-）小鼠存在高周转率骨质疏松症。这些结果表明，GIP不仅具有胰岛素调节作用，而且对脂肪组织的脂肪积累和骨骼的钙积累具有生理作用。我们在此提出一个新的首字母缩写GIP肠源性营养摄入多肽。

The hormonal factor(s) implicated as transmitters of signals from the gut to pancreatic β-cells is referred to incretin and gastric inhibitory polypeptide (GIP) is identified as one of the incretins. GIP is a gastrointestinal peptide hormone of 42 amino acids that is released from duodenal endocrine K-cells after absorption of glucose or fat and exerts its effects by binding to its specific receptor, the GIP receptors (GIPR). We have characterized mice with a targeted mutation of the GIPR gene and found that IRS-1(-/-)GIPR(-/-) mice exhibited both reduced adiposity and ameliorated insulin resistance, indicating 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. Furthermore, bone histomorphometrical analyses revealed that bone formation parameters were significantly lower and that the number of osteoclasts was significantly increased, indicating that GIP receptor(-/-) mice have high-turnover osteoporosis. These results indicated that GIP has not only an insulinotropic role but also physiological roles on fat-accumulation into adipose tissues and calcium-accumulation into bone. We here propose a new acronym GIP for Gut-derived nutrient-Intake Polypeptide.