{"title":"Catalyzing Diabetes Drug Discovery","authors":"","doi":"10.1126/scisignal.1922003tw287","DOIUrl":null,"url":null,"abstract":"One relatively unexplored drug target for type 2 diabetes is the glucose-sensing enzyme glucokinase (GK); mutations that reduce GK activity cause a rare inherited form of diabetes in humans. Grimsby et al. have identified a class of small molecules that allosterically activate GK. When orally administered to rodent models of type 2 diabetes, these compounds significantly improved glucose tolerance by enhancing glucose-dependent insulin secretion from the pancreas and by stimulating glucose utilization in the liver. J. Grimsby, R. Sarabu, W. L. Corbett, N.-E. Haynes, F. T. Bizzarro, J. W. Coffey, K. R. Guertin, D. W. Hilliard, R. F. Kester, P. E. Mahaney, L. Marcus, L. Qi, C. L. Spence, J. Tengi, M. A. Magnuson, C. A. Chu, M. T. Dvorozniak, F. M. Matschinsky, J. F. Grippo, Allosteric activators of glucokinase: Potential role in diabetes therapy. Science 301, 370-373 (2003). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"24 1","pages":"TW287 - tw287"},"PeriodicalIF":0.0000,"publicationDate":"2003-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science's STKE","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1126/scisignal.1922003tw287","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
One relatively unexplored drug target for type 2 diabetes is the glucose-sensing enzyme glucokinase (GK); mutations that reduce GK activity cause a rare inherited form of diabetes in humans. Grimsby et al. have identified a class of small molecules that allosterically activate GK. When orally administered to rodent models of type 2 diabetes, these compounds significantly improved glucose tolerance by enhancing glucose-dependent insulin secretion from the pancreas and by stimulating glucose utilization in the liver. J. Grimsby, R. Sarabu, W. L. Corbett, N.-E. Haynes, F. T. Bizzarro, J. W. Coffey, K. R. Guertin, D. W. Hilliard, R. F. Kester, P. E. Mahaney, L. Marcus, L. Qi, C. L. Spence, J. Tengi, M. A. Magnuson, C. A. Chu, M. T. Dvorozniak, F. M. Matschinsky, J. F. Grippo, Allosteric activators of glucokinase: Potential role in diabetes therapy. Science 301, 370-373 (2003). [Abstract] [Full Text]
2型糖尿病的一个相对未开发的药物靶点是葡萄糖感应酶葡萄糖激酶(GK);降低GK活性的突变导致一种罕见的人类遗传性糖尿病。Grimsby等人发现了一类能变构激活GK的小分子。当给2型糖尿病啮齿动物模型口服时，这些化合物通过增强胰腺葡萄糖依赖型胰岛素分泌和刺激肝脏葡萄糖利用，显著改善了葡萄糖耐量。J.格里姆斯比，R.萨拉布，W. L.科比特，n.e。Haynes, F. T. Bizzarro, J. W. Coffey, K. R. Guertin, D. W. Hilliard, R. F. Kester, P. E. Mahaney, L. Marcus, L. Qi, C. L. Spence, J. Tengi, M. A. Magnuson, C. A. Chu, M. T. Dvorozniak, F. M. Matschinsky, J. F. Grippo，葡萄糖激酶变张激活剂在糖尿病治疗中的潜在作用。科学通报，2004(3)。【摘要】【全文】
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
