Activation of NF-κB-Inducing Kinase in Islet β Cells Causes β Cell Failure and Diabetes
文献类型：期刊论文
| 作者 | Li, Xinzhi1; Wu, Yongsen1; Song, Yue1; Ding, Na1; Lu, Min1; Jia, Linna4; Zhao, Yujun2 ; Liu, Ming3; Chen, Zheng1
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| 刊名 | MOLECULAR THERAPY
 |
| 出版日期 | 2020-11-04 |
| 卷号 | 28期号:11页码:2430-2441 |
| ISSN号 | 1525-0016 |
| DOI | 10.1016/j.ymthe.2020.07.016 |
| 文献子类 | Article |
| 英文摘要 | Islet beta cell death has been proved to contribute to diabetes. Studies suggest that the activation of nuclear factor kappa B (NF-kappa B)-inducing kinase (NIK) is involved in the beta cell dysfunction encountered in obesity. However, the pathological significance of NIK activation in diabetes remains largely unknown. Here, we report that beta cell-specific overexpression of NIK (beta-NIK-OE) results in spontaneous diabetes in male mice at a young age (>= 10 weeks of age), which is likely due to insulin deficiency, beta cell death, and insulitis. Importantly, inhibiting the kinase activation of NIK by the small molecule B022 prevents NIK- or H2O2-induced beta cell death and also reduces streptozotocin (STZ)-induced beta cell death while ameliorating hyperglycemia, suggesting that the kinase activity of NIK is essential in inducing islet inflammation, beta cell death, and diabetes. In all, this study not only uncovers a role of NIK in beta cell failure but also provides a potential therapeutic target for the treatment of diabetes. |
| WOS关键词 | INFLAMMATION ; GLUCAGON ; ALPHA ; HYPERGLYCEMIA ; HYPOGLYCEMIA ; DYSFUNCTION ; OBESITY ; PATHWAY ; INSULIN |
| WOS研究方向 | Biotechnology & Applied Microbiology ; Genetics & Heredity ; Research & Experimental Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:000588103600013 |
| 出版者 | CELL PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309405]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Chen, Zheng |
| 作者单位 | 1.Harbin Inst Technol, Sch Life Sci & Technol, HIT Ctr Life Sci, Harbin 150001, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Meteria Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Tianjin Med Univ, Dept Endocrinol & Metab, Gen Hosp, Tianjin 300052, Peoples R China; 4.Northeast Normal Univ, Sch Life Sci, Minist Educ MOE, Key Lab Mol Epigenet, Changchun 130024, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Xinzhi,Wu, Yongsen,Song, Yue,et al. Activation of NF-κB-Inducing Kinase in Islet β Cells Causes β Cell Failure and Diabetes[J]. MOLECULAR THERAPY,2020,28(11):2430-2441. |
| APA | Li, Xinzhi.,Wu, Yongsen.,Song, Yue.,Ding, Na.,Lu, Min.,...&Chen, Zheng.(2020).Activation of NF-κB-Inducing Kinase in Islet β Cells Causes β Cell Failure and Diabetes.MOLECULAR THERAPY,28(11),2430-2441. |
| MLA | Li, Xinzhi,et al."Activation of NF-κB-Inducing Kinase in Islet β Cells Causes β Cell Failure and Diabetes".MOLECULAR THERAPY 28.11(2020):2430-2441. |
入库方式： OAI收割
来源：上海药物研究所
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