State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Department of Epidemiology, Fujian Medical University, Fuzhou, Fujian, China.
Curr Drug Targets. 2022;23(7):761-767. doi: 10.2174/1389450123666220303092324.
Diabetes mellitus (DM) is a common metabolic disorder characterized by a persistent increment of blood glucose. Type 2 DM is characterized by insulin resistance and β-cell dysfunction. Thioredoxin-interacting protein (TXNIP) is among the factors that control the production and loss of pancreatic β-cells.
Recent studies have shown that high glucose can significantly up-regulate the expression of the TXNIP. Overexpression of TXNIP in β-cells not only induced apoptosis but also decreased the production of insulin. At the same time, TXNIP deficiency protected the apoptosis of β-cells, leading to increased insulin production. Therefore, finding small molecules that can modulate TXNIP expression and downstream signalling pathways is essential. Thus, the inhibition of TXNIP has beneficial effects on the cardiovascular system and other tissues such as the heart and the kidney in DM. Therefore, DM treatment must target small TXNIP activity, inhibit expression, and promote endogenous cell mass and insulin production.
This review briefly describes the effect mechanism, regulatory mechanism, and crystal structure of TXNIP. In addition, we highlight how TXNIP signalling networks contribute to diabetes and interact with drugs that inhibit the development often and its complexes. Finally, the current status and prospects of TXNIP targeted therapy are also discussed.
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。2 型糖尿病的特征是胰岛素抵抗和β细胞功能障碍。硫氧还蛋白相互作用蛋白（TXNIP）是控制胰岛β细胞生成和丧失的因素之一。
最近的研究表明，高葡萄糖可以显著上调 TXNIP 的表达。TXNIP 在β细胞中的过表达不仅诱导细胞凋亡，还减少胰岛素的产生。同时，TXNIP 缺乏可保护β细胞凋亡，导致胰岛素产生增加。因此，寻找可以调节 TXNIP 表达和下游信号通路的小分子至关重要。因此，抑制 TXNIP 对糖尿病患者的心血管系统和心脏、肾脏等其他组织具有有益作用。因此，糖尿病的治疗必须针对 TXNIP 的活性，抑制其表达，并促进内源性细胞质量和胰岛素的产生。
本文简要描述了 TXNIP 的作用机制、调控机制和晶体结构。此外，还强调了 TXNIP 信号网络如何促进糖尿病的发展，并与抑制其复合物形成的药物相互作用。最后，还讨论了 TXNIP 靶向治疗的现状和前景。
