Xu Hanlin, Liu Tao, Dai Yanfen, Li Na, Cao Zhanqi
Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, China.
Front Pharmacol. 2025 May 9;16:1600251. doi: 10.3389/fphar.2025.1600251. eCollection 2025.
ERK1/2 (extracellular signal-regulated kinase 1/2) is an important member of the MAPK (mitogen-activated protein kinase) family and is widely involved in many biological processes such as cell proliferation, differentiation, apoptosis and migration. After activation by phosphorylation, ERK1/2 can be transferred into the nucleus and directly or indirectly affect the activity of transcription factors, thereby regulating gene expression. More and more studies have shown that ERK1/2 plays an important role in diabetes and its complications, such as insulin secretion, islet β cell function, diabetic cardiomyopathy, diabetic nephropathy, renal fibrosis, lipogenesis, diabetic vasculopathy, etc. These effects reveal the complexity and diversity of the ERK1/2 signaling pathway in the pathogenesis of diabetes, and its activation and inhibition mechanisms in multiple physiological and pathological processes provide potential targets for diabetes treatment. The purpose of this mini-review is to explore the key role of ERK1/2 in diabetes and the progress of research on targeted inhibitors of ERK1/2, which provides new strategies for the treatment of diabetes.
细胞外信号调节激酶1/2(ERK1/2)是丝裂原活化蛋白激酶(MAPK)家族的重要成员,广泛参与细胞增殖、分化、凋亡和迁移等多种生物学过程。磷酸化激活后,ERK1/2可转移至细胞核,直接或间接影响转录因子活性,从而调控基因表达。越来越多的研究表明,ERK1/2在糖尿病及其并发症中发挥重要作用,如胰岛素分泌、胰岛β细胞功能、糖尿病心肌病、糖尿病肾病、肾纤维化、脂肪生成、糖尿病血管病变等。这些作用揭示了ERK1/2信号通路在糖尿病发病机制中的复杂性和多样性,其在多种生理和病理过程中的激活和抑制机制为糖尿病治疗提供了潜在靶点。本综述的目的是探讨ERK1/2在糖尿病中的关键作用以及ERK1/2靶向抑制剂的研究进展,为糖尿病治疗提供新策略。