ETA as a novel Kv2.1 inhibitor ameliorates beta-cell dysfunction and hyperglycaemia
文献类型：期刊论文
| 作者 | Zhou, Tingting1,6; Du, Mengfan5; Zhao, Tong4; Quan, Lingling3; Zhu, Zhiyuan2; Chen, Jing1
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| 刊名 | CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
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| 出版日期 | 2018-12 |
| 卷号 | 45期号:12页码:1257-1264 |
| 关键词 | beta cell apoptosis glucose-stimulated insulin secretion T2DM |
| ISSN号 | 1440-1681 |
| DOI | 10.1111/1440-1681.13011 |
| 文献子类 | Article |
| 英文摘要 | The Kv2.1 channel plays an important role in the regulation against pancreatic beta-cell dysfunctions. Therefore, it is regarded as a promising target for drug discovery against type 2 diabetes. In the present study, we found that the small molecule 4-ethoxy-N-{[6-(2-thienyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl]methyl}aniline (ETA), a novel Kv2.1 inhibitor, may be capable of promoting glucose-stimulated insulin secretion and protecting from apoptosis in pancreatic INS-832/13 cells. The assay of ETA on type 2 diabetic mice induced by high-fat diet (HFD)/streptozocin (STZ) confirmed its potency in ameliorating glucose homeostasis. ETA administration reduced fasting blood glucose and glycated haemoglobin levels, improved oral glucose tolerance, and increased serum insulin levels in HFD/STZ mice. Mechanism study demonstrated that ETA protected INS-832/13 cells involving the regulation against protein kinase B and extracellular-regulated protein kinase 1/2 signalling pathways. Our study has confirmed the underlying regulation of Kv2.1 against beta-cell function and also addressed the potential of ETA as a lead compound in the treatment of type 2 diabetes mellitus. |
| WOS关键词 | INSULIN-SECRETION ; DIABETES-MELLITUS ; CHANNELS ; APOPTOSIS ; STREPTOZOTOCIN ; 3-KINASE/AKT ; PATHWAYS ; FAILURE ; ISLETS ; KINASE |
| 资助项目 | Suzhou science and technology project[SS201751] ; Fundamental Research Funds for the Central Universities[JUSRP11863] |
| WOS研究方向 | Pharmacology & Pharmacy ; Physiology |
| 语种 | 英语 |
| WOS记录号 | WOS:000450001800004 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279485]  |
| 专题 | 药物安全性评价中心 |
| 通讯作者 | Zhou, Tingting; Zhu, Zhiyuan; Chen, Jing |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Shanghai Jiao Tong Univ, Sch Med, Suzhou Kowloon Hosp, Cent Lab, 118 Wansheng St, Suzhou 215028, Peoples R China 3.Shanghai Normal Univ, Coll Life & Environm Sci, Shanghai, Peoples R China; 4.Nanjing Univ Chinese Med, Sch Med & Life Sci, State Key Lab Cultivat Base TCM Qual & Efficacy, Nanjing, Jiangsu, Peoples R China; 5.Jiangnan Univ, Sch Pharmaceut Sci, Wuxi, Peoples R China; 6.Jiangnan Univ, Wuxi Sch Med, 1800 Lihu Rd, Wuxi 214122, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhou, Tingting,Du, Mengfan,Zhao, Tong,et al. ETA as a novel Kv2.1 inhibitor ameliorates beta-cell dysfunction and hyperglycaemia[J]. CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY,2018,45(12):1257-1264. |
| APA | Zhou, Tingting,Du, Mengfan,Zhao, Tong,Quan, Lingling,Zhu, Zhiyuan,&Chen, Jing.(2018).ETA as a novel Kv2.1 inhibitor ameliorates beta-cell dysfunction and hyperglycaemia.CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY,45(12),1257-1264. |
| MLA | Zhou, Tingting,et al."ETA as a novel Kv2.1 inhibitor ameliorates beta-cell dysfunction and hyperglycaemia".CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY 45.12(2018):1257-1264. |
入库方式： OAI收割
来源：上海药物研究所
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