治疗糖尿病及其血管并发症的潜在新靶点——TXNIP

Thioredoxin-interacting protein: a new potential target for diabetes and related vascular complications therapy

硫氧还蛋白互作蛋白(thioredoxin-interacting protein,TXNIP),又称为维生素D_3上调蛋白(VDUP1),是硫氧还蛋白(thioredoxin,Trx)的内源性抑制剂,通过与Trx的结合与解离调节机体的氧化应激。TXNIP与葡萄糖毒性、热休克以及机械压力引起的细胞生长、凋亡和炎症有关,TXNIP的这些功能受到碳水化合物应答元件结合蛋白(carbohydrate response element binding protein,Ch REBP)以及AMP依赖的蛋白激酶(AMP-dependent protein kinase,AMPK)调节。近年来,大量研究显示TXNIP上调可能与糖尿病及并发症的发生密切相关。一方面,TXNIP可通过诱导胰岛素抵抗和增加肝葡萄糖的产生引起血糖紊乱;另一方面,葡萄糖是诱导TXNIP表达的最强生理刺激因子,增加的TXNIP又直接介导了葡萄糖引起的胰岛β细胞和内皮细胞的功能异常,因此TXNIP可能是导致糖尿病以及糖尿病血管性并发症的原因之一,未来有可能成为治疗糖尿病及其血管并发症的潜在靶点。

Thioredoxin-interacting protein （TXNIP）, also known as vitamin D3-up-regulated protein （VDUP1）, is an endogenous inhibitor of thioredoxin （Trx）, which regulates the cellular reduction-oxidation （redox） state. TXNIP regulates cellular survival, apoptosis and inflammation induced by glucotoxicity, heat shock and mechanical pressure. The above functions of TXNIP are regulated by carbohydrate response element binding protein （ChREBP） and AMP-dependent protein kinase （AMPK）. In recent years, numerous studies showed that TXNIP is involved in diabetes and diabetic complications. On the one hand, TXNIP functions in diabetes by increasing insulin resistance and hepatic gluconeogenesis. TXNIP expression is induced by high glucose, which is implicated in pancreatic beta cell glucotoxicity and endothelial cells dysfunction. TXNIP may contribute to the development and progression of diabetes and its vascular complications. TXNIP may be a new target for diabetes and its vascular complications therapy.