Abstract:
Diabetes Mellitus (DM) is one of the highest contributors to global mortality, exceeding numbers of even the three major infectious diseases in the world, namely Tuberculosis, HIV AIDS, and Malaria. DM is characterised by increased serum levels of glucose caused by a loss of beta cells of the pancreatic islets, responsible for the secretion of insulin. Upon accumulation of data via a wide array of literature surveys, it has been found that Thioredoxin Interacting Protein (TXNIP) presents itself as a vital factor in controlling the production and loss of beta islet cells. TXNIP inhibits the action of the Thioredoxin (TRX) protein found in the beta cells thereby rendering it ineffective in maintaining the cellular redox balance causing oxidative stress and subsequent consequences ultimately leading to aggravation of the disease. TRX exists in the form of two isoforms - TRX1, which is located in the cytosol and at times translocates to the nucleus, and TRX2, which is located in the nucleus. TRX is responsible for the maintenance of the normal cellular redox balance by reducing the oxidised proteins formed by the Reactive Oxygen Species (ROS) with the help of NADPH dependent TRX Reductase enzyme. This proves to be essential in the pathogenesis of Diabetes Mellitus as the beta cells of the pancreatic islets lack a sufficient amount of antioxidant systems. Thus, inhibition of TXNIP has become essential in the survival of beta cells, not only enhancing insulin secretion and sensitivity but also alleviating the diseases associated with Diabetes. Hence, TXNIP is discovered to be a unique therapeutic target in the management of DM.
摘要:
糖尿病(DM)是全球死亡率的最高贡献者之一,甚至超过世界三大传染病的数量,即结核病,艾滋病,和疟疾。DM的特征是由胰岛β细胞损失引起的血清葡萄糖水平升高,负责胰岛素的分泌。在通过广泛的文献调查积累数据后,已经发现硫氧还蛋白相互作用蛋白(TXNIP)在控制β胰岛细胞的产生和损失中表现为重要因素。TXNIP抑制β细胞中发现的硫氧还蛋白[TRX]蛋白的作用,从而使其在维持细胞氧化还原平衡方面无效,从而引起氧化应激和随后的后果,最终导致疾病加重。TRX以两种同工型的形式存在-TRX1,它位于细胞质中,有时易位到细胞核,和TRX2,它位于细胞核中。TRX通过在NADPH依赖性TRX还原酶的帮助下还原由活性氧(ROS)形成的氧化蛋白质来负责维持正常的细胞氧化还原平衡。这被证明在糖尿病的发病机理中是必需的,因为胰岛的β细胞缺乏足够量的抗氧化系统。因此,抑制TXNIP已成为β细胞存活的关键,不仅可以提高胰岛素分泌和敏感性,还可以缓解与糖尿病相关的疾病。因此,TXNIP被发现是DM管理中的独特治疗靶标。