摘要
背景和目的:硫氧还蛋白相互作用蛋白(TXNIP)也被称为硫氧还蛋白结合蛋白-2是一种普遍表达的蛋白质,其相互作用并负调节硫氧还蛋白(TXN)的表达和功能。在过去几年中,由于其广泛的功能影响了能量代谢的几个方面,TXNIP引起了相当大的关注。 TXNIP通过多效性作用,作为葡萄糖和脂质代谢的重要调节因子,包括调节β细胞功能,肝葡萄糖产生,外周葡萄糖摄取,脂肪形成和底物利用。动物模型中TXNIP的过度表达已被证明可诱导胰腺β细胞的凋亡,降低外周组织如骨骼肌和脂肪的胰岛素敏感性,并降低能量消耗。相反,TXNIP缺陷动物受到饮食诱导的胰岛素抵抗和2型糖尿病的保护。 总结:因此,目标TXNIP被认为提供新的治疗机会,并且TXNIP抑制剂有潜力成为治疗糖尿病的有力治疗工具。在这里,我们总结了我们对TXNIP生物学的了解的现状,突出了其在代谢调节中的作用,并提出了有助于未来研究利用TXNIP作为治疗靶点的关键问题。
关键词: 糖尿病,硫氧还蛋白系统,硫氧还蛋白相互作用蛋白,氧化应激,胰岛素抵抗,胰腺β细胞功能障碍,代谢稳态
Current Drug Targets
Title:TXNIP in Metabolic Regulation: Physiological Role and Therapeutic Outlook
Volume: 18 Issue: 9
关键词: 糖尿病,硫氧还蛋白系统,硫氧还蛋白相互作用蛋白,氧化应激,胰岛素抵抗,胰腺β细胞功能障碍,代谢稳态
摘要: Background & Objective: Thioredoxin-interacting protein (TXNIP) also known as thioredoxin binding protein-2 is a ubiquitously expressed protein that interacts and negatively regulates expression and function of Thioredoxin (TXN). Over the last few years, TXNIP has attracted considerable attention due to its wide-ranging functions impacting several aspects of energy metabolism. TXNIP acts as an important regulator of glucose and lipid metabolism through pleiotropic actions including regulation of β-cell function, hepatic glucose production, peripheral glucose uptake, adipogenesis, and substrate utilization. Overexpression of TXNIP in animal models has been shown to induce apoptosis of pancreatic β-cells, reduce insulin sensitivity in peripheral tissues like skeletal muscle and adipose, and decrease energy expenditure. On the contrary, TXNIP deficient animals are protected from diet induced insulin resistance and type 2 diabetes.
Summary: Consequently, targeting TXNIP is thought to offer novel therapeutic opportunity and TXNIP inhibitors have the potential to become a powerful therapeutic tool for the treatment of diabetes mellitus. Here we summarize the current state of our understanding of TXNIP biology, highlight its role in metabolic regulation and raise critical questions that could help future research to exploit TXNIP as a therapeutic target.Export Options
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Cite this article as:
TXNIP in Metabolic Regulation: Physiological Role and Therapeutic Outlook, Current Drug Targets 2017; 18 (9) . https://dx.doi.org/10.2174/1389450118666170130145514
DOI https://dx.doi.org/10.2174/1389450118666170130145514 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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