Kitaura Hideki, Ogawa Saika, Ohori Fumitoshi, Noguchi Takahiro, Marahleh Aseel, Nara Yasuhiko, Pramusita Adya, Kinjo Ria, Ma Jinghan, Kanou Kayoko, Mizoguchi Itaru
Division of Orthodontics and Dentofacial Orthopedics, Graduate School of Dentistry, Tohoku University, 4-1, Seiryo-machi, Aoba-ku, Miyagi, Sendai 980-8575, Japan.
Int J Mol Sci. 2021 Jun 19;22(12):6578. doi: 10.3390/ijms22126578.
Patients with type 2 diabetes have an increased risk of fracture compared to the general population. Glucose absorption is accelerated by incretin hormones, which induce insulin secretion from the pancreas. The level of the incretin hormone, glucagon-like peptide-1 (GLP-1), shows an immediate postprandial increase, and the circulating level of intact GLP-1 is reduced rapidly by dipeptidyl peptidase-4 (DPP-4)-mediated inactivation. Therefore, GLP-1 receptor agonists and DPP-4 inhibitors are effective in the treatment of type 2 diabetes. However, these incretin-related diabetic agents have been reported to affect bone metabolism, including bone formation and resorption. These agents enhance the expression of bone markers, and have been applied to improve bone quality and bone density. In addition, they have been reported to suppress chronic inflammation and reduce the levels of inflammatory cytokine expression. Previously, we reported that these incretin-related agents inhibited both the expression of inflammatory cytokines and inflammation-induced bone resorption. This review presents an overview of current knowledge regarding the effects of incretin-related diabetes drugs on osteoblast differentiation and bone formation as well as osteoclast differentiation and bone resorption. The mechanisms by which incretin-related diabetes drugs regulate bone formation and bone resorption are also discussed.
与普通人群相比，2型糖尿病患者骨折风险增加。肠促胰岛素激素可加速葡萄糖吸收，该激素能诱导胰腺分泌胰岛素。肠促胰岛素激素胰高血糖素样肽-1（GLP-1）的水平在餐后立即升高，而完整GLP-1的循环水平会因二肽基肽酶-4（DPP-4）介导的失活作用而迅速降低。因此，GLP-1受体激动剂和DPP-4抑制剂在2型糖尿病治疗中有效。然而，据报道这些与肠促胰岛素相关的糖尿病药物会影响骨代谢，包括骨形成和骨吸收。这些药物可增强骨标志物的表达，并已被用于改善骨质量和骨密度。此外，据报道它们可抑制慢性炎症并降低炎症细胞因子表达水平。此前，我们报道这些与肠促胰岛素相关的药物既能抑制炎症细胞因子的表达，又能抑制炎症诱导的骨吸收。本综述概述了目前关于与肠促胰岛素相关的糖尿病药物对成骨细胞分化和骨形成以及破骨细胞分化和骨吸收影响的相关知识。还讨论了与肠促胰岛素相关的糖尿病药物调节骨形成和骨吸收的机制。
