The role of GRB2 in diabetes, diabetes complications and related disorders.

IF 5.4 2区医学 Q1 ENDOCRINOLOGY & METABOLISM Diabetes, Obesity & Metabolism Pub Date : 2024-10-30 DOI:10.1111/dom.16015

Jing Ma, Yuyan Dong, Juxiang Liu, Shuo Gao, Jinxing Quan

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Abstract

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.

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GRB2 在糖尿病、糖尿病并发症和相关疾病中的作用。

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适配蛋白，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。糖尿病并发症大大降低了患者的预期寿命和生活质量，给社会造成了沉重负担。然而，GRB2 在糖尿病及相关并发症中的作用在很大程度上还不为人所知。新的证据表明，GRB2 在胰岛素抵抗、炎症、免疫激活以及细胞增殖、生长、新陈代谢、血管生成、凋亡和分化等细胞过程的调控中发挥着至关重要的作用。GRB2 介导的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恶化。本综述全面概述了目前对 GRB2 在糖尿病、糖尿病并发症和相关疾病中作用的理解，以及 GRB2 靶向疗法的最新进展。阐明GRB2在这些疾病中的复杂作用为针对GRB2介导的通路的潜在治疗策略提供了宝贵的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetes, Obesity & Metabolism 医学-内分泌学与代谢

CiteScore

10.90

自引率

6.90%

发文量

319

审稿时长

3-8 weeks

期刊介绍： Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.