AICAR and Metformin Exert AMPK-dependent Effects on INS-1E Pancreatic beta-cell Apoptosis via Differential Downstream Mechanisms
文献类型：期刊论文
| 作者 | Dai, Yu-Lu; Huang, Su-Ling ; Leng, Ying
|
| 刊名 | INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
 |
| 出版日期 | 2015 |
| 卷号 | 11期号:11页码:1272-1280 |
| 关键词 | AICAR Metformin AMPK INS-1E cells apoptosis |
| ISSN号 | 1449-2288 |
| DOI | 10.7150/ijbs.12108 |
| 文献子类 | Article |
| 英文摘要 | The role of AMP-activated protein kinase (AMPK) in pancreatic beta -cell apoptosis is still controversial, and the reasons for the discrepancies have not been clarified. In the current study, we observed the effects of two well-known AMPK activators 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and metformin, on apoptosis in rat insulinoma INS-1E cells, and further explored their possible mechanisms. Both AICAR and metformin protected INS-1E cells from palmitate-induced apoptosis, as reflected by decreases in both cleaved caspase 3 protein expression and caspase 3/7 activity, and these protective effects were abrogated by AMPK inhibitor compound C. The protective action of AICAR was probably mediated by the suppression of triacylglycerol accumulation, increase in Akt phosphorylation and decrease in p38 MAPK phosphorylation, while metformin might exert its protective effect on INS-1E cells by decreases in both JNK and p38 MAPK phosphorylation. All these regulations were dependent on AMPK activation. However, under standard culture condition, AICAR increased JNK phosphorylation and promoted INS-1E cell apoptosis in an AMPK-dependent manner, whereas metformin showed no effect on apoptosis. Our study revealed that AMPK activators AICAR and metformin exhibited different effects on INS-1E cell apoptosis under different culture conditions, which might be largely attributed to different downstream mediators. Our results provided new and informative clues for better understanding of the role of AMPK in beta-cell apoptosis. |
| WOS关键词 | ACTIVATED PROTEIN-KINASE ; ENDOPLASMIC-RETICULUM STRESS ; MITOCHONDRIAL DYSFUNCTION ; SIGNALING PATHWAY ; GLUCOLIPOTOXICITY ; STIMULATION ; FAILURE ; GLUCOSE ; ISLETS ; RATS |
| 资助项目 | National Nature Science Foundation of China[81202570] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000363677500004 |
| 出版者 | IVYSPRING INT PUBL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276695]  |
| 专题 | 药理学第一研究室 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 |
| 通讯作者 | Leng, Ying |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Dai, Yu-Lu,Huang, Su-Ling,Leng, Ying. AICAR and Metformin Exert AMPK-dependent Effects on INS-1E Pancreatic beta-cell Apoptosis via Differential Downstream Mechanisms[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,2015,11(11):1272-1280. |
| APA | Dai, Yu-Lu,Huang, Su-Ling,&Leng, Ying.(2015).AICAR and Metformin Exert AMPK-dependent Effects on INS-1E Pancreatic beta-cell Apoptosis via Differential Downstream Mechanisms.INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,11(11),1272-1280. |
| MLA | Dai, Yu-Lu,et al."AICAR and Metformin Exert AMPK-dependent Effects on INS-1E Pancreatic beta-cell Apoptosis via Differential Downstream Mechanisms".INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 11.11(2015):1272-1280. |
入库方式： OAI收割
来源：上海药物研究所
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