DC260126: A Small-Molecule Antagonist of GPR40 that Protects against Pancreatic beta-Cells Dysfunction in db/db Mice
文献类型：期刊论文
| 作者 | Sun, Peng; Wang, Ting; Zhou, Yuren; Liu, Hong ; Jiang, Hualiang; Zhu, Weiliang; Wang, Heyao
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| 刊名 | PLOS ONE
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| 出版日期 | 2013-06-11 |
| 卷号 | 8期号:6 |
| ISSN号 | 1932-6203 |
| DOI | 10.1371/journal.pone.0066744 |
| 文献子类 | Article |
| 英文摘要 | G protein-coupled receptor 40 (GPR40) mediates both acute and chronic effects of free fatty acids (FFAs) on insulin secretion. However, it remains controversial whether inhibition of GPR40 would be beneficial in prevention of type 2 diabetes. This study is designed to evaluate the potential effects of DC260126, a small molecule antagonist of GPR40, on beta-cell function following administration of 10 mg/kg dose of DC260126 to obese diabetic db/db mice. Oral glucose tolerance test, glucose stimulated insulin secretion and insulin tolerance test were used to investigate the pharmacological effects of DC260126 on db/db mice after 21-days treatment. Immunohistochemistry and serum biochemical analysis were also performed in this study. Although no significant change of blood glucose levels was found in DC260126-treated mice, DC260126 significantly inhibited glucose stimulated insulin secretion, reduced blood insulin level and improved insulin sensitivity after 3 weeks administration in db/db mice. Moreover, DC260126 reduced the proinsulin/insulin ratio and the apoptotic rate of pancreatic beta-cells remarkably in DC260126-treated db/db mice compared to vehicle-treated mice (p<0.05, n = 8). The results suggest that although DC260126 could not provide benefit for improving hyperglycemia, it could protect against pancreatic b-cells dysfunction through reducing overload of beta-cells, and it increases insulin sensitivity possibly via alleviation of hyperinsulinemia in db/db mice. |
| WOS关键词 | FREE FATTY-ACIDS ; STIMULATED INSULIN-SECRETION ; ENDOPLASMIC-RETICULUM STRESS ; IMPAIRED GLUCOSE-TOLERANCE ; IN-VIVO ; ELEVATED GLUCOSE ; RECEPTOR GPR40 ; DIABETIC MICE ; ER STRESS ; PALMITATE |
| 资助项目 | National Nature Science Foundation of China[81072681] ; National High Technology Research and Development Program of China (863 Program)[2007AA02Z301] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000320755400155 |
| 出版者 | PUBLIC LIBRARY SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277585]  |
| 专题 | 药物发现与设计中心 药理学第三研究室 上海中药现代化研究中心 |
| 通讯作者 | Zhu, Weiliang |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Sun, Peng,Wang, Ting,Zhou, Yuren,et al. DC260126: A Small-Molecule Antagonist of GPR40 that Protects against Pancreatic beta-Cells Dysfunction in db/db Mice[J]. PLOS ONE,2013,8(6). |
| APA | Sun, Peng.,Wang, Ting.,Zhou, Yuren.,Liu, Hong.,Jiang, Hualiang.,...&Wang, Heyao.(2013).DC260126: A Small-Molecule Antagonist of GPR40 that Protects against Pancreatic beta-Cells Dysfunction in db/db Mice.PLOS ONE,8(6). |
| MLA | Sun, Peng,et al."DC260126: A Small-Molecule Antagonist of GPR40 that Protects against Pancreatic beta-Cells Dysfunction in db/db Mice".PLOS ONE 8.6(2013). |
入库方式： OAI收割
来源：上海药物研究所
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