摘要
背景:糖尿病(DM)是一种常见的代谢紊乱,其特征是血糖持续升高。2型糖尿病的特点是胰岛素抵抗和β细胞功能障碍。硫氧还蛋白相互作用蛋白(TXNIP)是控制胰腺β-细胞产生和丢失的因素之一。 目的:近期研究表明,高糖可显著上调TXNIP的表达。TXNIP在β细胞中过表达不仅能诱导细胞凋亡,还能减少胰岛素的分泌。同时,TXNIP缺乏保护β细胞凋亡,导致胰岛素分泌增加。因此,寻找可以调节TXNIP表达和下游信号通路的小分子是至关重要的。因此,抑制TXNIP对糖尿病患者心血管系统及心脏、肾脏等组织均有有益作用。因此,糖尿病治疗必须针对TXNIP的小分子活性,抑制表达,促进内源性细胞数量和胰岛素的产生。 结论:本文综述了TXNIP的作用机制、调控机制及晶体结构。此外,我们强调了TXNIP信号网络如何促进糖尿病,并与抑制糖尿病发展的药物相互作用及其复合物。最后,对TXNIP靶向治疗的现状和前景进行了展望。
关键词: TXNIP、β细胞、DM、FOXO1、ChREBP、胰岛素。
图形摘要
[http://dx.doi.org/10.4239/wjd.v6.i6.850] [PMID: 26131326]
[http://dx.doi.org/10.2174/1573399812666160614123226] [PMID: 27306960]
[http://dx.doi.org/10.2174/1573399812666151016101622] [PMID: 26472574]
[http://dx.doi.org/10.1016/S0140-6736(13)60591-7] [PMID: 23890997]
[http://dx.doi.org/10.2174/1573399814666180730105351] [PMID: 30058495]
[http://dx.doi.org/10.5001/omj.2012.68] [PMID: 23071876]
[http://dx.doi.org/10.2174/1573399815666191024085838] [PMID: 31657690]
[http://dx.doi.org/10.2174/1573399812666151020101222] [PMID: 28917077]
[http://dx.doi.org/10.4239/wjd.v6.i8.1065] [PMID: 26240703]
[http://dx.doi.org/10.2174/1573399054022776] [PMID: 18220596]
[http://dx.doi.org/10.1210/me.2014-1095] [PMID: 24911120]
[http://dx.doi.org/10.1016/0167-4781(94)90242-9] [PMID: 8086474]
[http://dx.doi.org/10.1074/jbc.274.31.21645] [PMID: 10419473]
[http://dx.doi.org/10.1006/bbrc.2000.2699] [PMID: 10814541]
[http://dx.doi.org/10.4049/jimmunol.164.12.6287] [PMID: 10843682]
[http://dx.doi.org/10.1080/15216540252774739] [PMID: 11795589]
[http://dx.doi.org/10.1074/jbc.M600427200] [PMID: 16766796]
[http://dx.doi.org/10.1038/ni.1831] [PMID: 20023662]
[http://dx.doi.org/10.1158/0008-5472.CAN-03-0908] [PMID: 14983878]
[http://dx.doi.org/10.1210/en.2008-0646] [PMID: 18974273]
[http://dx.doi.org/10.2174/1389450118666170130145514] [PMID: 28137209]
[http://dx.doi.org/10.2174/1573399815666190510112035] [PMID: 31074371]
[http://dx.doi.org/10.1503/cmaj.060244] [PMID: 16847277]
[http://dx.doi.org/10.5897/JPAP2013.0001]
[http://dx.doi.org/10.2174/1573408016999200801021329]
[http://dx.doi.org/10.3233/JAD-180814] [PMID: 30741672]
[http://dx.doi.org/10.3233/JAD-180735] [PMID: 30372683]
[http://dx.doi.org/10.1007/s10787-021-00861-4] [PMID: 34350508]
[http://dx.doi.org/10.1155/2016/2386068]
[http://dx.doi.org/10.1073/pnas.1414859111] [PMID: 25313054]
[http://dx.doi.org/10.1016/j.cca.2012.03.021] [PMID: 22521751]
[http://dx.doi.org/10.1111/febs.14926] [PMID: 31090171]
[http://dx.doi.org/10.1371/journal.pmed.0040158] [PMID: 17472435]
[http://dx.doi.org/10.1074/jbc.M708169200] [PMID: 17998203]
[http://dx.doi.org/10.1074/jbc.M115.698365] [PMID: 26858253]
[http://dx.doi.org/10.1210/en.2004-1378] [PMID: 15705778]
[http://dx.doi.org/10.1038/nm.3287] [PMID: 23975026]
[http://dx.doi.org/10.1074/jbc.M109.034421] [PMID: 19959470]
[http://dx.doi.org/10.1074/jbc.M114.592360] [PMID: 25391656]
[http://dx.doi.org/10.1074/jbc.M113.525022] [PMID: 24627476]
[http://dx.doi.org/10.1152/physrev.00042.2009] [PMID: 21742788]
[http://dx.doi.org/10.1016/j.febslet.2013.01.017] [PMID: 23337872]
[http://dx.doi.org/10.2337/db11-0802] [PMID: 22586588]
[http://dx.doi.org/10.1007/s00125-012-2506-4] [PMID: 22382520]
[http://dx.doi.org/10.1371/journal.pone.0008397] [PMID: 20027290]
[http://dx.doi.org/10.1371/journal.pone.0022544] [PMID: 21811631]
[http://dx.doi.org/10.1016/j.tem.2013.01.003] [PMID: 23597489]
[http://dx.doi.org/10.1074/jbc.M801539200] [PMID: 18591247]
[http://dx.doi.org/10.1074/jbc.M113.473082] [PMID: 23803610]
[http://dx.doi.org/10.1016/j.tem.2011.05.003] [PMID: 21719305]
[http://dx.doi.org/10.2174/138945011796150262] [PMID: 21443465]
[http://dx.doi.org/10.2174/1573399811666150804104858] [PMID: 26239835]
[http://dx.doi.org/10.2174/092986709788802980] [PMID: 19689288]
[http://dx.doi.org/10.2174/1573399811666141216160217] [PMID: 25515340]
[http://dx.doi.org/10.1038/ncomms3958] [PMID: 24389582]
[http://dx.doi.org/10.1042/BJ20150830] [PMID: 26527736]
[http://dx.doi.org/10.1161/CIRCRESAHA.114.301315] [PMID: 24515523]
[http://dx.doi.org/10.1172/JCI87382] [PMID: 27500491]