Ma Jing, Dong Yuyan, Liu Juxiang, Gao Shuo, Quan Jinxing
Department of Endocrinology and Metabolism, Gansu Provincial Hospital, The First Clinical Medical School, Lanzhou University, Lanzhou, China.
Department of Endocrinology and Metabolism, Gansu Provincial Hospital, Lanzhou, China.
Diabetes Obes Metab. 2025 Jan;27(1):23-34. doi: 10.1111/dom.16015. Epub 2024 Oct 30.
Growth factor receptor-bound protein 2 (GRB2) is a key adaptor protein involved in multiple signalling pathways, and its dysregulation is associated with various diseases. Type 2 diabetes is a systemic condition characterized by insulin resistance and impaired β-cell function. The complications of diabetes significantly reduce life expectancy and quality of life, imposing a substantial burden on society. However, the role of GRB2 in diabetes and associated complications is largely unknown. Emerging evidence suggests that GRB2 plays a crucial role in insulin resistance, inflammation, immune activation and the regulation of cellular processes such as cell proliferation, growth, metabolism, angiogenesis, apoptosis and differentiation. Dysregulation of GRB2-mediated pathways contributes to the progression of diabetic neuropathy, cognitive dysfunction, nephropathy, retinopathy and related disorders. This review provides a comprehensive overview of the current understanding of the role of GRB2 in diabetes, diabetes complications and related disorders, alongside recent advances in the development of GRB2-targeted therapies. Elucidating the complex role of GRB2 in these disorders provides valuable insights into potential therapeutic strategies targeting GRB2-mediated pathways.
生长因子受体结合蛋白2(GRB2)是一种参与多种信号通路的关键衔接蛋白,其失调与多种疾病相关。2型糖尿病是一种以胰岛素抵抗和β细胞功能受损为特征的全身性疾病。糖尿病并发症显著降低预期寿命和生活质量,给社会带来沉重负担。然而,GRB2在糖尿病及其相关并发症中的作用在很大程度上尚不清楚。新出现的证据表明,GRB2在胰岛素抵抗、炎症、免疫激活以及细胞增殖、生长、代谢、血管生成、凋亡和分化等细胞过程的调节中起关键作用。GRB2介导的信号通路失调会导致糖尿病神经病变、认知功能障碍、肾病、视网膜病变及相关疾病的进展。本综述全面概述了目前对GRB2在糖尿病、糖尿病并发症及相关疾病中的作用的理解,以及GRB2靶向治疗开发的最新进展。阐明GRB2在这些疾病中的复杂作用为针对GRB2介导的信号通路的潜在治疗策略提供了有价值的见解。