Glucose-dependent insulinotropic polypeptide receptor knockout mice have altered bone turnover
Glucose-dependent insulinotropic polypeptide receptor knockout mice have altered bone turnover
复制标题
DOI：
10.1016/j.bone.2005.06.021
复制
发表时间：
2005-12-01
期刊：
影响因子：
4.1
通讯作者：
Isales, CM
中科院分区：
文献类型：
--
作者：
Xie, D;Cheng, H;Isales, CM
葡萄糖依赖性促胰岛素多肽（GIP）是一种肠促胰岛素激素，由餐后小肠内分泌细胞分泌。 GIP 已被证明可以在体外影响成骨细胞功能；然而，GIP 对骨重塑的体内作用仍不清楚。在本研究中，我们通过评估 GIP 受体敲除小鼠（GIPR-/- 小鼠）的骨转换血清标志物、骨密度、骨形态以及生物力学骨强度随时间（1 至 5 个月）的变化，研究了 GIP 在调节骨转换中的作用。 GIPR-/-小鼠表现出骨尺寸减小、骨量降低、骨微结构和生物力学特性改变以及骨转换参数改变，尤其是在骨形成方面。此外，GIP对骨量的影响是位点特异性的，并且随着时间的推移而形成补偿机制，并改善了GIP信号丢失对骨量的影响。此外，GIPR-/-小鼠的身体成分（包括骨量、去脂体重和脂肪百分比）比野生型小鼠更早出现与年龄相关的变化。总之，我们的结果表明 GIP 对骨量和骨质量具有合成代谢作用，并表明 GIP 可能是营养物质摄入和利用之间的激素联系。 (c) 2005 Elsevier Inc. 保留所有权利。
Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone, which is secreted from endocrine cells in the small intestine after meal ingestion. GIP has been shown to affect osteoblastic function in vitro; however, the in vivo effects of GIP on bone remodeling remain unclear. In the present study, we investigated the role of GIP in modulating bone turnover, by evaluating serum markers of bone turnover, bone density, bone morphology, and changes in biomechanical bone strength over time (one to five months) in GIP receptor knockout mice (GIPR-/- mice). The GIPR-/- mice showed a decreased bone size, lower bone mass, altered bone microarchitecture and biomechanical properties, and altered parameters for bone turnover, especially in bone formation. Moreover, the effects of GIP on bone mass were site-specific and compensatory mechanism developed over time and ameliorated the impact of the loss of GIP signaling on bone mass. Further, GIPR-/- mice had earlier age-related changes than wild-type mice in body composition, including bone mass, lean body mass, and fat percentage. In summary, our results indicate that GIP has an anabolic effect on bone mass and bone quality and suggests that GIP may be a hormonal link between nutrient ingestion and utilization. (c) 2005 Elsevier Inc. All rights reserved.