Current Advances in the Biochemical and Physiological Aspects of the Treatment of Type 2 Diabetes Mellitus with Thiazolidinediones.
Current Advances in the Biochemical and Physiological Aspects of the Treatment of Type 2 Diabetes Mellitus with Thiazolidinediones.
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DOI：
10.1155/2016/7614270
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发表时间：
2016
期刊：
影响因子：
2.9
通讯作者：
Mendieta-Wejebe JE
中科院分区：
文献类型：
--
作者：
Alemán-González-Duhart D;Tamay-Cach F;Álvarez-Almazán S;Mendieta-Wejebe JE
本文综述了噻唑烷二酮类药物（TZDs）治疗2型糖尿病（DM2）的生理生化方面的研究进展。DM2是一种以高血糖为特征的代谢紊乱，触发葡萄糖自氧化、多元醇途径、糖基化末端（AGE）产物形成和糖酵解等生理通路的异常激活，导致活性氧（ROS）和促炎细胞因子的过量产生，导致该疾病的微血管和大血管并发症。DM2的治疗一直是通过使用不同的药物来降低高血糖，如胰岛素增敏剂，如tzd，它能够通过与核过氧化物酶体增殖激活受体γ (PPARγ)结合作为完全激动剂来降低血糖水平和循环甘油三酯。当TZDs与PPARγ相互作用时，该受体调节参与葡萄糖稳态、胰岛素抵抗和脂肪形成的不同基因的转录。然而，tzd有一些副作用，如液体潴留、体重增加、肝毒性、血浆容量扩张、血液稀释、水肿、骨折和充血性心力衰竭，这限制了它们在DM2患者中的应用。
The present review summarizes the current advances in the biochemical and physiological aspects in the treatment of type 2 diabetes mellitus (DM2) with thiazolidinediones (TZDs). DM2 is a metabolic disorder characterized by hyperglycemia, triggering the abnormal activation of physiological pathways such as glucose autooxidation, polyol's pathway, formation of advance glycation end (AGE) products, and glycolysis, leading to the overproduction of reactive oxygen species (ROS) and proinflammatory cytokines, which are responsible for the micro- and macrovascular complications of the disease. The treatment of DM2 has been directed toward the reduction of hyperglycemia using different drugs such as insulin sensitizers, as the case of TZDs, which are able to lower blood glucose levels and circulating triglycerides by binding to the nuclear peroxisome proliferator-activated receptor gamma (PPARγ) as full agonists. When TZDs interact with PPARγ, the receptor regulates the transcription of different genes involved in glucose homeostasis, insulin resistance, and adipogenesis. However, TZDs exhibit some adverse effects such as fluid retention, weight gain, hepatotoxicity, plasma-volume expansion, hemodilution, edema, bone fractures, and congestive heart failure, which limits their use in DM2 patients.