Department of Pathophysiology, Medical College, Nanchang University, Jiangxi Province Key Laboratory of Tumor Pathogenesis and Molecular Pathology, 461 Bayi Road, Nanchang 330006, China.
Int J Mol Sci. 2019 Jan 6;20(1):179. doi: 10.3390/ijms20010179.
Cdc42, a member of the Rho GTPases family, is involved in the regulation of several cellular functions including cell cycle progression, survival, transcription, actin cytoskeleton organization and membrane trafficking. Diabetes is a chronic and metabolic disease, characterized as glycometabolism disorder induced by insulin deficiency related to β cell dysfunction and peripheral insulin resistance (IR). Diabetes could cause many complications including diabetic nephropathy (DN), diabetic retinopathy and diabetic foot. Furthermore, hyperglycemia can promote tumor progression and increase the risk of malignant cancers. In this review, we summarized the regulation of Cdc42 in insulin secretion and diabetes-associated diseases. Organized researches indicate that Cdc42 is a crucial member during the progression of diabetes, and Cdc42 not only participates in the process of insulin synthesis but also regulates the insulin granule mobilization and cell membrane exocytosis via activating a series of downstream factors. Besides, several studies have demonstrated Cdc42 as participating in the pathogenesis of IR and DN and even contributing to promote cancer cell proliferation, survival, invasion, migration, and metastasis under hyperglycemia. Through the current review, we hope to cast light on the mechanism of Cdc42 in diabetes and associated diseases and provide new ideas for clinical diagnosis, treatment, and prevention.
Cdc42 是 Rho GTPases 家族的成员,参与调节多种细胞功能,包括细胞周期进程、存活、转录、肌动蛋白细胞骨架组织和膜运输。糖尿病是一种慢性代谢性疾病,其特征为胰岛素缺乏相关的β细胞功能障碍和外周胰岛素抵抗(IR)引起的糖代谢紊乱。糖尿病可导致多种并发症,包括糖尿病肾病(DN)、糖尿病性视网膜病变和糖尿病足。此外,高血糖可促进肿瘤进展并增加恶性癌症的风险。在这篇综述中,我们总结了 Cdc42 在胰岛素分泌和糖尿病相关疾病中的调节作用。有组织的研究表明,Cdc42 是糖尿病进展过程中的关键成员,Cdc42 不仅参与胰岛素的合成过程,还通过激活一系列下游因子来调节胰岛素颗粒的动员和细胞膜胞吐作用。此外,几项研究表明,Cdc42 参与了 IR 和 DN 的发病机制,甚至在高血糖下有助于促进癌细胞的增殖、存活、侵袭、迁移和转移。通过本次综述,我们希望阐明 Cdc42 在糖尿病及其相关疾病中的作用机制,并为临床诊断、治疗和预防提供新的思路。