Novel approaches to drug discovery for the treatment of type 2 diabetes.
Novel approaches to drug discovery for the treatment of type 2 diabetes.
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治疗 2 型糖尿病的药物发现新方法。
DOI：
10.1517/17460441.2014.941352
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Shen X
中科院分区：
文献类型：
--
作者：
Xu X;Wang G;Zhou T;Chen L;Chen J;Shen X
简介：2型糖尿病（T2DM）是一种慢性、复杂、多因素的代谢性疾病，已成为严重的全球健康问题。已知药物的副作用和长期安全性数据的缺乏，加上目前针对T2DM的临床前药物已确定的不良反应，在很大程度上呼吁迫切探索针对该疾病的新型治疗和预防策略。涵盖领域：作者强调了抗 T2DM 药物发现的潜在方法，重点关注：胰腺 β 细胞质量的恢复、胰岛素分泌的促进、氧化应激和内质网 (ER) 应激的调节以及自噬的调节。专家观点：T2DM是基于胰岛素抵抗和β细胞功能障碍的逐渐发展。因此，β细胞功能的恢复被认为是对抗T2DM的有前途的治疗策略之一。氧化应激、内质网应激和自噬等应激因素在 T2DM 发生过程中对 β 细胞凋亡、胰岛素分泌和敏感性的调节中发挥着重要作用，涉及复杂的交叉对话。基于多重应激调控网络，越来越多的新的潜在靶点被发现，多靶点药物先导物有望帮助开发更有效的治疗T2DM的临床药物。
Introduction: Type 2 diabetes mellitus (T2DM) is a chronic, complex and multifactorial metabolic disorder, which has become a serious global health problem. The side effects of known drugs and the deficiency of long-term safety data, in addition to the already determined adverse effects for the current preclinical drugs against T2DM, have largely called upon the urgent exploration of novel therapeutic and preventative strategies against this disease. Areas covered: The authors highlight the potential approaches for anti-T2DM drug discovery by focusing on: the restoration of pancreatic β-cell mass, the promotion of insulin secretion, the regulation of oxidative stress and endoplasmic reticulum (ER) stress and the modulation of autophagy. Expert opinion: T2DM is based on the gradual development of insulin resistance and β-cell dysfunction. Thus, the restoration of β-cell function is considered as one of the promising therapeutic strategies against T2DM. The stress factors, such as oxidative stress, ER stress and autophagy, play potent roles in the regulation of β-cell apoptosis, insulin secretion and sensitivity in the development of T2DM involving complicated cross-talks. Based on multiplex stress-involved regulatory networks, more and more novel potential targets have been discovered and the multi-targeted drug leads are expected to help develop more effective clinical agents for the treatment of T2DM.