Latanoprost effectively ameliorates glucose and lipid disorders in db/db and ob/ob mice
文献类型：期刊论文
| 作者 | Wang, Gaihong; Xu, Xing; Yao, Xingang; Zhu, Zhiyuan; Yu, Liang ; Chen, Lili; Chen, Jing; Shen, Xu
|
| 刊名 | DIABETOLOGIA
 |
| 出版日期 | 2013-12 |
| 卷号 | 56期号:12页码:2702-2712 |
| 关键词 | AMPK Glucose and lipid metabolism Latanoprost RXR alpha/PPAR gamma heterodimer Type 2 diabetes |
| ISSN号 | 0012-186X |
| DOI | 10.1007/s00125-013-3032-8 |
| 文献子类 | Article |
| 英文摘要 | Improvement of glucose and lipid metabolic dysfunctions is a potent therapeutic strategy against type 2 diabetes mellitus, and identifying new functions for existing drugs may help accelerate the speed of new drug development. Here, we report that latanoprost, a clinical drug for treating primary open-angle glaucoma and intraocular hypertension, effectively ameliorated glucose and lipid disorders in two mouse models of type 2 diabetes. In addition, the glucose-lowering mechanisms of latanoprost were intensively investigated. A binding-affinity assay and enzymatic tests were used to determine the targets of latanoprost. Cell-based assays on 3T3-L1 adipocytes and C2C12 myotubes and animal model-based assays with db/db and ob/ob mice were further performed to clarify the mechanisms underlying latanoprost-regulated glucose and lipid metabolism. Latanoprost functioned as both an indirect activator of AMP-activated protein kinase and a selective retinoid X receptor alpha (RXR alpha) antagonist able to selectively antagonise the transcription of a RXR alpha/peroxisome proliferator-activated receptor gamma heterodimer. It promoted glucose uptake, inhibited pre-adipocyte differentiation and regulated the main genes responsible for glucose and lipid metabolism, including Fas, Scd1, Perilipin (also known as Plin1), Lpl and Pdk4. Chronic administration of latanoprost in mice potently decreased the levels of fasting blood glucose, HbA(1c), fructosamine (FMN), NEFA and total cholesterol, and effectively improved glucose tolerance and glucose/lipid metabolism-related genes in vivo. Our studies demonstrate that the existing eye drug latanoprost is both an indirect activator of AMP-activated protein kinase and a selective RXR alpha antagonist. Latanoprost effectively ameliorated glucose and lipid disorders in diabetic mice, which strongly highlights the potential of latanoprost in the treatment of type 2 diabetes mellitus. |
| WOS关键词 | ACTIVATED PROTEIN-KINASE ; ACETYL-COA CARBOXYLASE ; DIET-INDUCED OBESITY ; PPAR-GAMMA ; INSULIN-RESISTANCE ; RECEPTOR-GAMMA ; METABOLIC SYNDROME ; HEPATIC STEATOSIS ; FAT ; ROSIGLITAZONE |
| 资助项目 | National Science and Technology Major Project[2012ZX09103101-018] ; State Key Program of Basic Research of People's Republic of China[2010CB912501] ; National Natural Science Foundation of People's Republic of China[81173105] ; National Natural Science Foundation of People's Republic of China[81220108025] ; National Natural Science Foundation of People's Republic of China[91213306] ; Foundation of Chinese Academy of Sciences[KSCX2-EW-Q-3] |
| WOS研究方向 | Endocrinology & Metabolism |
| 语种 | 英语 |
| WOS记录号 | WOS:000326599300020 |
| 出版者 | SPRINGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277367]  |
| 专题 | 药物安全性评价中心 药理学第三研究室 |
| 通讯作者 | Chen, Jing |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Gaihong,Xu, Xing,Yao, Xingang,et al. Latanoprost effectively ameliorates glucose and lipid disorders in db/db and ob/ob mice[J]. DIABETOLOGIA,2013,56(12):2702-2712. |
| APA | Wang, Gaihong.,Xu, Xing.,Yao, Xingang.,Zhu, Zhiyuan.,Yu, Liang.,...&Shen, Xu.(2013).Latanoprost effectively ameliorates glucose and lipid disorders in db/db and ob/ob mice.DIABETOLOGIA,56(12),2702-2712. |
| MLA | Wang, Gaihong,et al."Latanoprost effectively ameliorates glucose and lipid disorders in db/db and ob/ob mice".DIABETOLOGIA 56.12(2013):2702-2712. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。