Ramsey Walter, Isales Carlos M
Institute for Regenerative and Reparative Medicine, Augusta University, Augusta, GA, 30912, USA.
Department of Neuroscience and Regenerative Medicine, Augusta University, Augusta, GA, 30912, USA.
Adv Exp Med Biol. 2017;1033:13-33. doi: 10.1007/978-3-319-66653-2_2.
Although originally identified as modulators of nutrient absorption, the gut hormones gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon-like peptide-2 (GLP-2) have also been found to play an important role in the regulation of bone turnover. These "incretin" hormones promote bone anabolism by stimulating osteoblast differentiation as well as increasing osteoblast longevity. In addition, GIP and perhaps GLP-2 attenuate the activity of osteoclastic cells, leading to a net increase in bone deposition and ultimately increasing bone mass. Studies have demonstrated that these hormones are important for bone mineralization and overall bone quality and function evolutionarily as important nutritional links signaling nutrient availability for skeletal anabolic functions. Accordingly, these entero-osseous hormones (EOH) have therapeutic potential for the management of osteoporosis. Although this chapter primarily focuses on skeletal effects of these incretin hormones, the GIP, GLP-1, and GLP-2 receptors are actually widely expressed throughout the body. Therefore, we will also briefly discuss these extraosseous receptors/effects and how they may indirectly impact the skeleton.
尽管最初被确定为营养吸收的调节因子，但肠道激素胃抑制多肽（GIP）、胰高血糖素样肽-1（GLP-1）和胰高血糖素样肽-2（GLP-2）也被发现对骨转换的调节起着重要作用。这些“肠促胰岛素”激素通过刺激成骨细胞分化以及延长成骨细胞寿命来促进骨合成代谢。此外，GIP以及可能还有GLP-2会减弱破骨细胞的活性，导致骨沉积净增加并最终增加骨量。研究表明，这些激素对骨矿化以及整体骨质量和功能在进化上作为向骨骼合成代谢功能发出营养可用性信号的重要营养联系至关重要。因此，这些肠骨激素（EOH）在骨质疏松症的管理方面具有治疗潜力。尽管本章主要关注这些肠促胰岛素激素对骨骼的影响，但GIP、GLP-1和GLP-2受体实际上在全身广泛表达。因此，我们也将简要讨论这些骨外受体/效应以及它们如何可能间接影响骨骼。
