申请人:Hotamisligil Gökhan S.
公开号:US20100075894A1
公开(公告)日:2010-03-25
Endoplasmic reticulum stress has been found to be associated with obesity. Therefore, agents that reduce or prevent ER stress may be used to treat diseases associated with obesity including peripheral insulin resistance, hypergylcemia, and type 2 diabetes. Two compounds which have been shown to reduce ER stress and to reduce blood glucose levels include 4-phenyl butyric acid (PBA), tauroursodeoxycholic acid (TUDCA), and trimethylamine N-oxide (TMAO). Other compounds useful in reducing ER stress are chemical chaperones such as trimethylamine N-oxide and glycerol. The present invention provides methods of treating a subject suffering from obesity, hyperglycemia, type 2 diabetes, or insulin resistance using ER stress reducers such as PBA, TUDCA, and TMAO. Methods of screening for ER stress reducers by identifying agents that reduce levels of ER stress markers in ER stressed cells are also provided. These agents may find use in methods and pharmaceutical compositions for treating obesity-associated diseases.
内质网应激与肥胖有关。因此,减少或防止内质网应激的药物可用于治疗与肥胖相关的疾病,包括外周胰岛素抵抗、高血糖和2型糖尿病。已经显示出减少内质网应激并降低血糖水平的两种化合物包括4-苯基丁酸(PBA)、牛磺胆酸(TUDCA)和三甲胺氧化物(TMAO)。其他有用于减少内质网应激的化合物是化学分子伴侣,例如三甲胺氧化物和甘油。本发明提供了使用内质网应激减轻剂如PBA、TUDCA和TMAO治疗患有肥胖、高血糖、2型糖尿病或胰岛素抵抗的受试者的方法。还提供了通过识别减少内质网应激标志物水平的药物筛选内质网应激减轻剂的方法。这些药物可用于治疗与肥胖相关的疾病的方法和制药组合物。