Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia.
Centre for Drug and Herbal Development, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia.
Int J Mol Sci. 2023 Aug 4;24(15):12441. doi: 10.3390/ijms241512441.
A positive association between insulin resistance and osteoporosis has been widely established. However, crosstalk between the signalling molecules in insulin and Wingless (Wnt)/beta-(β-)catenin transduction cascades orchestrating bone homeostasis remains not well understood. The current review aims to collate the existing evidence, reporting (a) the expression of insulin signalling molecules involved in bone-related disorders and (b) the expression of Wnt/β-catenin signalling molecules involved in governing insulin homeostasis. The downstream effector molecule, glycogen synthase kinase-3 beta (GSK3β), has been identified to be a point of convergence linking the two signal transduction networks. This review highlights that GSK3β may be a drug target in the development of novel anabolic agents and the potential use of GSK3β inhibitors to treat bone-related disorders.
胰岛素抵抗与骨质疏松之间存在正相关关系,这已得到广泛证实。然而,调节骨稳态的胰岛素和 Wnt/β-连环蛋白信号转导级联中的信号分子之间的串扰仍不太清楚。本综述旨在汇集现有证据,报告(a)参与骨相关疾病的胰岛素信号分子的表达和(b)参与调节胰岛素稳态的 Wnt/β-连环蛋白信号分子的表达。下游效应分子糖原合酶激酶-3β(GSK3β)已被确定为连接两个信号转导网络的交汇点。本综述强调,GSK3β 可能是开发新型合成代谢药物的靶点,以及潜在使用 GSK3β 抑制剂治疗骨相关疾病。