Department of Endocrinology and Metabolism, Odense University Hospital (OUH), Odense C, Denmark.
The Molecular Endocrinology & Stem Cell Research Unit, OUH & University of Southern Denmark, Odense C, Denmark.
Basic Clin Pharmacol Toxicol. 2018 Jan;122(1):25-37. doi: 10.1111/bcpt.12850. Epub 2017 Aug 11.
The relationship between gut and skeleton is increasingly recognized as part of the integrated physiology of the whole organism. The incretin hormones gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted from the intestine in response to nutrient intake and exhibit several physiological functions including regulation of islet hormone secretion and glucose levels. A number of GLP-1 receptor agonists (GLP-1RAs) are currently used in treatment of type 2 diabetes and obesity. However, GIP and GLP-1 cognate receptors are widely expressed suggesting that incretin hormones mediate effects beyond control of glucose homeostasis, and reports on associations between incretin hormones and bone metabolism have emerged. The aim of this MiniReview was to provide an overview of current knowledge regarding the in vivo and in vitro effects of GIP and GLP-1 on bone metabolism. We identified a total of 30 pre-clinical and clinical investigations of the effects of GIP, GLP-1 and GLP-1RAs on bone turnover markers, bone mineral density (BMD), bone microarchitecture and fracture risk. Studies conducted in cell cultures and rodents demonstrated that GIP and GLP-1 play a role in regulating skeletal homeostasis, with pre-clinical data suggesting that GIP inhibits bone resorption whereas GLP-1 may promote bone formation and enhance bone material properties. These effects are not corroborated by clinical studies. While there is evidence of effects of GIP and GLP-1 on bone metabolism in pre-clinical investigations, clinical trials are needed to clarify whether similar effects are present and clinically relevant in humans.
肠道和骨骼之间的关系正日益被视为整个机体综合生理学的一部分。肠泌素激素胃抑制多肽(GIP)和胰高血糖素样肽-1(GLP-1)在响应营养摄入时从肠道中分泌,并表现出多种生理功能,包括调节胰岛激素分泌和葡萄糖水平。一些 GLP-1 受体激动剂(GLP-1RAs)目前用于治疗 2 型糖尿病和肥胖症。然而,GIP 和 GLP-1 同源受体广泛表达,表明肠泌素激素介导的作用超出了对葡萄糖稳态的控制,并且关于肠泌素激素与骨代谢之间的关联的报告已经出现。本综述的目的是提供关于 GIP 和 GLP-1 对骨代谢的体内和体外作用的当前知识概述。我们总共确定了 30 项关于 GIP、GLP-1 和 GLP-1RAs 对骨转换标志物、骨密度(BMD)、骨微结构和骨折风险影响的临床前和临床研究。在细胞培养和啮齿动物中进行的研究表明,GIP 和 GLP-1 在调节骨骼稳态中发挥作用,临床前数据表明 GIP 抑制骨吸收,而 GLP-1 可能促进骨形成并增强骨材料特性。这些作用与临床研究并不相符。虽然有证据表明 GIP 和 GLP-1 对骨代谢有影响,但需要进行临床试验以阐明在人类中是否存在类似的作用及其临床相关性。
Basic Clin Pharmacol Toxicol. 2017-8-11
Morphologie. 2017-3
Diabetes Obes Metab. 2016-6-7
Clin Calcium. 2009-9
Diabetologia. 2023-10
J Diabetes Investig. 2016-3-31
J Endocrinol. 2024-10-1
Nutrients. 2021-9-14
Int J Mol Sci. 2021-6-19
Endocr Rev. 2021-11-16