DGAT1 inhibitors protect pancreatic beta-cells from palmitic acid-induced apoptosis
文献类型：期刊论文
| 作者 | Huang, Jun-shang1,2; Guo, Bin-bin2; Wang, Gai-hong2; Zeng, Li-min2; Hu, You-hong1,2 ; Wang, Ting2; Wang, He-yao1,2
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2020-07-31 |
| 页码 | 8 |
| 关键词 | type 2 diabetes DGAT1 inhibitors pancreatic beta-cells apoptosis ER stress inflammation |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/s41401-020-0482-7 |
| 通讯作者 | Wang, Ting(wangting@simm.ac.cn) ; Wang, He-yao(hywang@simm.ac.cn) |
| 英文摘要 | Previous studies demonstrated that prolonged exposure to elevated levels of free fatty acids (FFA), especially saturated fatty acids, could lead to pancreatic beta-cell apoptosis, which plays an important role in the progression of type 2 diabetes (T2D). Diacylglycerol acyltransferase 1 (DGAT1), an enzyme that catalyzes the final step of triglyceride (TG) synthesis, has been reported as a novel target for the treatment of multiple metabolic diseases. In this study we evaluated the potential beneficial effects of DGAT1 inhibitors on pancreatic beta-cells, and further verified their antidiabetic effects in db/db mice. We showed that DGAT1 inhibitors (4aand LCQ908) at the concentration of 1 mu M significantly ameliorated palmitic acid (PA)-induced apoptosis in MIN6 pancreatic beta-cells and primary cultured mouse islets; oral administration of a DGAT1 inhibitor (4a) (100 mg/kg) for 4 weeks significantly reduced the apoptosis of pancreatic islets indb/dbmice. Meanwhile,4aadministration significantly decreased fasting blood glucose and TG levels, and improved glucose tolerance and insulin tolerance indb/dbmice. Furthermore, we revealed that pretreatment with 4a(1 mu M) significantly alleviated PA-induced intracellular lipid accumulation, endoplasmic reticulum (ER) stress, and proinflammatory responses in MIN6 cells, which might contribute to the protective effects of DGAT1 inhibitors on pancreatic beta-cells. These findings provided a better understanding of the antidiabetic effects of DGAT1 inhibitors. |
| WOS关键词 | ISOLATED RAT ISLETS ; INDUCED ER STRESS ; TRIGLYCERIDE SYNTHESIS ; FATTY-ACID ; INSULIN-RESISTANCE ; LIPOTOXICITY ; DYSFUNCTION ; OBESITY ; EXPRESSION ; SECRETION |
| 资助项目 | National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002-002-007] ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development, the Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12040336] ; National Natural Science Foundation of China[81503124] ; National Natural Science Foundation of China[81773791] ; National Natural Science Foundation of China[81473262] ; Institutes for Drug Discovery and Development, Chinese Academy of Sciences[CASIMM0120162025] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000554332300001 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/292205]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Wang, Ting; Wang, He-yao |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Huang, Jun-shang,Guo, Bin-bin,Wang, Gai-hong,et al. DGAT1 inhibitors protect pancreatic beta-cells from palmitic acid-induced apoptosis[J]. ACTA PHARMACOLOGICA SINICA,2020:8. |
| APA | Huang, Jun-shang.,Guo, Bin-bin.,Wang, Gai-hong.,Zeng, Li-min.,Hu, You-hong.,...&Wang, He-yao.(2020).DGAT1 inhibitors protect pancreatic beta-cells from palmitic acid-induced apoptosis.ACTA PHARMACOLOGICA SINICA,8. |
| MLA | Huang, Jun-shang,et al."DGAT1 inhibitors protect pancreatic beta-cells from palmitic acid-induced apoptosis".ACTA PHARMACOLOGICA SINICA (2020):8. |
入库方式： OAI收割
来源：上海药物研究所
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