Ravindran Sivasree, Wong Sok Kuan, Mohamad Nur-Vaizura, Chin Kok-Yong
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.
Biomedicines. 2025 Jun 19;13(6):1504. doi: 10.3390/biomedicines13061504.
Insulin, a key hormone primarily involved in glucose metabolism, has emerged as a crucial modulator of bone metabolism. Increasing evidence suggests that insulin influences bone health, but its precise mechanism of action remains unestablished. This review explores the intricate relationship between insulin and bone health, as well as elucidating the mechanism of action involved. Animal models of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) demonstrated distinct skeletal alterations, largely attributed to differences in insulin availability and associated metabolic dysfunction. Insulin deficiency in T1DM was associated with the deterioration of trabecular and cortical bone, whereas insulin resistance in T2DM primarily compromised trabecular bone quality. The route, frequency, and duration of insulin administration have been shown to influence bone-related outcomes. Studies involving insulin receptor silencing have suggested that insulin signalling is essential for normal bone development and maintenance. In humans, inconsistent findings on the effects of circulating insulin levels and insulin resistance on bone health were mainly attributed to heterogeneity in age, gender, metabolic status, study designs, population characteristics, and assessment methods. This review also highlights current knowledge gaps and underscores the need for longitudinal studies and mechanistic research. A clearer understanding of the insulin-bone axis may guide the development of targeted strategies to mitigate skeletal complications in individuals with diabetes mellitus.
胰岛素是主要参与葡萄糖代谢的关键激素，已成为骨代谢的重要调节因子。越来越多的证据表明胰岛素会影响骨骼健康，但其确切作用机制尚未明确。本综述探讨了胰岛素与骨骼健康之间的复杂关系，并阐明其中涉及的作用机制。1型糖尿病（T1DM）和2型糖尿病（T2DM）的动物模型表现出明显的骨骼改变，这在很大程度上归因于胰岛素可用性及相关代谢功能障碍的差异。T1DM中的胰岛素缺乏与小梁骨和皮质骨的恶化有关，而T2DM中的胰岛素抵抗主要损害小梁骨质量。胰岛素给药的途径、频率和持续时间已被证明会影响与骨相关的结果。涉及胰岛素受体沉默的研究表明，胰岛素信号传导对于正常骨骼发育和维持至关重要。在人类中，关于循环胰岛素水平和胰岛素抵抗对骨骼健康影响的研究结果不一致，这主要归因于年龄、性别、代谢状态、研究设计、人群特征和评估方法的异质性。本综述还强调了当前的知识空白，并强调了纵向研究和机制研究的必要性。对胰岛素-骨轴的更清晰理解可能会指导制定有针对性的策略，以减轻糖尿病患者的骨骼并发症。
