High-Throughput Screening for GPR119 Modulators Identifies a Novel Compound with Anti-Diabetic Efficacy in db/db Mice
文献类型：期刊论文
| 作者 | Zhang, Meng2; Feng, Yang2; Wang, Jia1 ; Zhao, Jianwei1; Li, Ting2; He, Min1; Yang, Dehua2; Nosjean, Olivier3; Boutin, Jean3; Renard, Pierre3
|
| 刊名 | PLOS ONE
 |
| 出版日期 | 2013-05-21 |
| 卷号 | 8期号:5 |
| ISSN号 | 1932-6203 |
| DOI | 10.1371/journal.pone.0063861 |
| 文献子类 | Article |
| 英文摘要 | G protein-coupled receptor 119 (GPR119) is highly expressed in pancreatic beta cells and enteroendocrine cells. It is involved in glucose-stimulated insulin secretion and glucagon-like peptide-1 (GLP-1) release, thereby representing a promising target for the treatment of type 2 diabetes. Although a number of GPR119 agonists were developed, no positive allosteric modulator (PAM) to this receptor has been reported. Here we describe a high-throughput assay for screening GPR119 PAMs and agonists simultaneously. Following screening of a small molecule compound library containing 312,000 synthetic and natural product-derived samples, one potent GPR119 agonist with novel chemical structure, MW1219, was identified. Exposure of MIN6 and GLUTag cells to MW1219 enhanced glucose-stimulated insulin secretion and GLP-1 release; once-daily oral dosing of MW1219 for 6 weeks in diabetic db/db mice reduced hemoglobin A1c (HbA1c) and improved plasma glucose, insulin and GLP-1 levels; it also increased glucose tolerance. The results demonstrate that MW1219 is capable of effectively controlling blood glucose level and may have the potential to be developed as a new class of anti-diabetic agents. |
| WOS关键词 | GLUCAGON-LIKE PEPTIDE-1 ; GLYCEMIC CONTROL ; RECEPTOR ; AGONISTS ; G-PROTEIN-COUPLED-RECEPTOR-119 ; PATHOGENESIS ; SECRETION ; DISCOVERY ; RELEASE ; NIDDM |
| 资助项目 | Ministry of Health of China[2012ZX09304011] ; Ministry of Health of China[2013ZX09507002] ; Shanghai Science and Technology Development Fund[11DZ2292200] ; Les Laboratories Servier (France)[00000000] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000319330200077 |
| 出版者 | PUBLIC LIBRARY SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277614]  |
| 专题 | 国家新药筛选中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药物制剂研究中心 |
| 通讯作者 | Wang, Ming-Wei |
| 作者单位 | 1.Chinese Natl Cpd Lib, Shanghai, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 200031, Peoples R China; 3.Les Labs Servier, Neuilly Sur Seine, France |
| 推荐引用方式 GB/T 7714 | Zhang, Meng,Feng, Yang,Wang, Jia,et al. High-Throughput Screening for GPR119 Modulators Identifies a Novel Compound with Anti-Diabetic Efficacy in db/db Mice[J]. PLOS ONE,2013,8(5). |
| APA | Zhang, Meng.,Feng, Yang.,Wang, Jia.,Zhao, Jianwei.,Li, Ting.,...&Wang, Ming-Wei.(2013).High-Throughput Screening for GPR119 Modulators Identifies a Novel Compound with Anti-Diabetic Efficacy in db/db Mice.PLOS ONE,8(5). |
| MLA | Zhang, Meng,et al."High-Throughput Screening for GPR119 Modulators Identifies a Novel Compound with Anti-Diabetic Efficacy in db/db Mice".PLOS ONE 8.5(2013). |
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。