RNA-binding protein CUGBP1 regulates insulin secretion via activation of phosphodiesterase 3B in mice
文献类型：期刊论文
| 作者 | Zhai, Kui2; Gu, Lei2; Yang, Zhiguang2; Mao, Yang2; Jin, Meng2; Chang, Yan2; Yuan, Qi2; Leblais, Veronique1; Wang, Huiwen2,3; Fischmeister, Rodolphe1 |
| 刊名 | DIABETOLOGIA
 |
| 出版日期 | 2016-09 |
| 卷号 | 59期号:9页码:1959-1967 |
| 关键词 | cAMP CUGBP1 Insulin secretion PDE3B RNA-binding protein Type 2 diabetes |
| ISSN号 | 0012-186X |
| DOI | 10.1007/s00125-016-4005-5 |
| 文献子类 | Article |
| 英文摘要 | Aims/hypothesis CUG-binding protein 1 (CUGBP1) is a multifunctional RNA-binding protein that regulates RNA processing at several stages including translation, deadenylation and alternative splicing, as well as RNA stability. Recent studies indicate that CUGBP1 may play a role in metabolic disorders. Our objective was to examine its role in endocrine pancreas function through gain-and loss-of-function experiments and to further decipher the underlying molecular mechanisms. Methods A mouse model in which type 2 diabetes was induced by a high-fat diet (HFD; 60% energy from fat) and mice on a standard chow diet (10% energy from fat) were compared. Pancreas-specific CUGBP1 overexpression and knockdown mice were generated. Different lengths of the phosphodiesterase subtype 3B (PDE3B) 3' untranslated region (UTR) were cloned for luciferase reporter analysis. Purified CUGBP1 protein was used for gel shift experiments. Results CUGBP1 is present in rodent islets and in beta cell lines; it is overexpressed in the islets of diabetic mice. Compared with control mice, the plasma insulin level after a glucose load was significantly lower and glucose clearance was greatly delayed in mice with pancreas-specific CUGBP1 overexpression; the opposite results were obtained upon pancreas-specific CUGBP1 knockdown. Glucose-and glucagon-like peptide1 (GLP-1)-stimulated insulin secretion was significantly attenuated in mouse islets upon CUGBP1 overexpression. This was associated with a strong decrease in intracellular cAMP levels, pointing to a potential role for cAMP PDEs. CUGBP1 overexpression had no effect on the mRNA levels of PDE1A, 1C, 2A, 3A, 4A, 4B, 4D, 7A and 8B subtypes, but resulted in increased PDE3B expression. CUGBP1 was found to directly bind to a specific ATTTGTT sequence residing in the 3' UTR of PDE3B and stabilised PDE3B mRNA. In the presence of the PDE3 inhibitor cilostamide, glucose-and GLP-1-stimulated insulin secretion was no longer reduced by CUGBP1 overexpression. Similar to CUGBP1, PDE3B was overexpressed in the islets of diabetic mice. Conclusions/interpretation We conclude that CUGBP1 is a critical regulator of insulin secretion via activating PDE3B. Repressing this protein might provide a potential strategy for treating type 2 diabetes. |
| WOS关键词 | MYOTONIC-DYSTROPHY TYPE-1 ; ELAV-LIKE FAMILY ; BETA-CELL ; PANCREATIC-ISLETS ; GLUCOSE ; OVEREXPRESSION ; RESISTANCE ; HEART ; MECHANISMS ; EXOCYTOSIS |
| 资助项目 | National Basic Research Programme of China[2011CB809104] ; National Foundation of Sciences and Technology[31371430] ; State Key Laboratory of Drug Research[SIMM1501KF-12] |
| WOS研究方向 | Endocrinology & Metabolism |
| 语种 | 英语 |
| WOS记录号 | WOS:000380668800020 |
| 出版者 | SPRINGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275920]  |
| 专题 | 新药研究国家重点实验室 中科院受体结构与功能重点实验室 |
| 通讯作者 | Fischmeister, Rodolphe; Ji, Guangju |
| 作者单位 | 1.Univ Paris 11, INSERM, UMR S 1180, Fac Pharm, 5 Rue JB Clement, F-92296 Chatenay Malabry, France; 2.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhai, Kui,Gu, Lei,Yang, Zhiguang,et al. RNA-binding protein CUGBP1 regulates insulin secretion via activation of phosphodiesterase 3B in mice[J]. DIABETOLOGIA,2016,59(9):1959-1967. |
| APA | Zhai, Kui.,Gu, Lei.,Yang, Zhiguang.,Mao, Yang.,Jin, Meng.,...&Ji, Guangju.(2016).RNA-binding protein CUGBP1 regulates insulin secretion via activation of phosphodiesterase 3B in mice.DIABETOLOGIA,59(9),1959-1967. |
| MLA | Zhai, Kui,et al."RNA-binding protein CUGBP1 regulates insulin secretion via activation of phosphodiesterase 3B in mice".DIABETOLOGIA 59.9(2016):1959-1967. |
入库方式： OAI收割
来源：上海药物研究所
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