Study on metabolism in vivo mediated by gut hormone

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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.