Wondafrash Dawit Zewdu, Nire'a Asmelash Tesfay, Tafere Gebrehiwot Gebremedihn, Desta Desilu Mahari, Berhe Demoze Asmerom, Zewdie Kaleab Alemayehu
Department of Pharmacology and Toxicology, School of Pharmacy, Mekelle University, Mekelle, Ethiopia.
Pharmacology and Toxicology Research and Course Unit, Department of Pharmacy, Axum University, Axum, Ethiopia.
Diabetes Metab Syndr Obes. 2020 Jan 7;13:43-51. doi: 10.2147/DMSO.S232221. eCollection 2020.
Diabetes mellitus (DM) is a common metabolic disorder which is characterized by a persistent increment of blood glucose. Globally, DM affects millions of people and the prevalence is increasing alarmingly. The critical step in the pathophysiology of DM is the loss of β-cells of the pancreas, which are responsible for the secretion of insulin. Thioredoxin-interacting protein (TXNIP) is among the factors that control the production and loss of the pancreatic β-cells. TXNIP is an α-arrestin that can bind and inhibit thioredoxin (the antioxidant protein) which is produced in the pancreatic islet after glucose intake. Numerous studies illustrated that elevated TXNIP levels were found to induce β-cell apoptosis; whereas TXNIP deficiency protects against type I and type II diabetes by promoting β-cell survival. Nowadays, TXNIP depletion is becoming a key factor in pancreatic β-cell survival enhancement. In the present review, targeting TXNIP is found to be relevant as a unique therapeutic opportunity, not only to improve insulin secretion and sensitivity, but also ameliorating the long term microvascular and macrovascular complications of the disease. Thus, TXNIP inhibitors that could reduce the expression and/or activity of TXNIP to non-diabetic levels are promising agents to halt the alarming rate of diabetes and its related complications.
糖尿病（DM）是一种常见的代谢紊乱疾病，其特征是血糖持续升高。在全球范围内，糖尿病影响着数百万人，且患病率正以惊人的速度上升。糖尿病病理生理学的关键步骤是胰腺β细胞的丧失，而胰腺β细胞负责胰岛素的分泌。硫氧还蛋白相互作用蛋白（TXNIP）是控制胰腺β细胞产生和丧失的因素之一。TXNIP是一种α-抑制蛋白，它能结合并抑制硫氧还蛋白（抗氧化蛋白），硫氧还蛋白是在摄入葡萄糖后在胰岛中产生的。大量研究表明，TXNIP水平升高会诱导β细胞凋亡；而TXNIP缺乏则通过促进β细胞存活来预防I型和II型糖尿病。如今，TXNIP缺失正成为增强胰腺β细胞存活的关键因素。在本综述中，发现靶向TXNIP作为一种独特的治疗机会具有相关性，不仅可以改善胰岛素分泌和敏感性，还能改善该疾病的长期微血管和大血管并发症。因此，能够将TXNIP的表达和/或活性降低至非糖尿病水平的TXNIP抑制剂是有望阻止糖尿病及其相关并发症惊人发生率的药物。
