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糖尿病与并发症:细胞信号通路、当前认识及靶向治疗

Diabetes and Complications: Cellular Signaling Pathways, Current Understanding and Targeted Therapies.

作者信息

Adeshara Krishna A, Diwan Arundhati G, Tupe Rashmi S

机构信息

Biochemical Sciences Division, Rajiv Gandhi Institute of IT and Biotechnology, Bharati Vidyapeeth University, Pune-411 046, India.

出版信息

Curr Drug Targets. 2016;17(11):1309-28. doi: 10.2174/1389450117666151209124007.

Abstract

Diabetes is a metabolic disorder and over the past decades, it has become a major cause of morbidity and mortality affecting the youth and middle-aged as it is the fourth leading cause of disease related to death. In both type 1 and type 2 diabetes the severe pathogenesis cause micro vascular complications: nephropathy, retinopathy, neuropathy and macro vascular complications: cardiovascular disease, heart attacks and stroke. Under hyperglycemia, activation of different signaling mechanisms such as an increased polyol pathway, advanced-glycation end product formation, activation of Protein Kinase C and hexosamine pathway leads to the over expression of reactive oxygen species and causes pathogenesis of diabetic complications. It is necessary to understand these pathways in diabetic complications causing damage to the secondary system of the body. In the past decade the understanding of these biochemical changes has increased tremendously and various molecules have been exploited as therapeutic targets for diabetic complications as better therapeutic approach. In this review, a brief overview about diabetes mellitus and chronic complications with their current understandings of cellular/molecular mechanisms and targeted therapies along with novel therapeutic strategies is discussed.

摘要

糖尿病是一种代谢紊乱疾病,在过去几十年里,它已成为影响青年和中年人群发病和死亡的主要原因,是与死亡相关疾病的第四大主要病因。在1型和2型糖尿病中,严重的发病机制都会引发微血管并发症,如肾病、视网膜病变、神经病变,以及大血管并发症,如心血管疾病、心脏病发作和中风。在高血糖情况下,不同信号传导机制的激活,如多元醇途径增加、晚期糖基化终产物形成、蛋白激酶C激活和己糖胺途径激活,会导致活性氧的过度表达,并引发糖尿病并发症的发病机制。了解这些导致身体二级系统受损的糖尿病并发症途径很有必要。在过去十年里,对这些生化变化的认识有了极大提高,各种分子已被用作糖尿病并发症的治疗靶点,作为更好的治疗方法。在这篇综述中,我们将简要概述糖尿病及其慢性并发症,以及目前对细胞/分子机制的理解、靶向治疗和新的治疗策略。

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