2. Academic Validation
  3. Activation of NF-κB-Inducing Kinase in Islet β Cells Causes β Cell Failure and Diabetes

Activation of NF-κB-Inducing Kinase in Islet β Cells Causes β Cell Failure and Diabetes

  • Mol Ther. 2020 Nov 4;28(11):2430-2441. doi: 10.1016/j.ymthe.2020.07.016.
Xinzhi Li 1,  Yongsen Wu 1,  Yue Song 1,  Na Ding 1,  Min Lu 1,  Linna Jia 2,  Yujun Zhao 3,  Ming Liu 4,  Zheng Chen 5
Affiliations

Affiliations

  • 1 HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China.
  • 2 Key Laboratory of Molecular Epigenetics of the Ministry of Education (MOE), School of Life Sciences, Northeast Normal University, Changchun 130024, China.
  • 3 State Key Laboratory of Drug Research, Shanghai Institute of Meteria Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • 4 Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin 300052, China.
  • 5 HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China. Electronic address: chenzheng@hit.edu.cn.
PMID: 32730745 DOI: 10.1016/j.ymthe.2020.07.016
Abstract

Islet β cell death has been proved to contribute to diabetes. Studies suggest that the activation of nuclear factor κB (NF-κB)-inducing kinase (NIK) is involved in the β cell dysfunction encountered in obesity. However, the pathological significance of NIK activation in diabetes remains largely unknown. Here, we report that β cell-specific overexpression of NIK (β-NIK-OE) results in spontaneous diabetes in male mice at a young age (≥10 weeks of age), which is likely due to Insulin deficiency, β cell death, and insulitis. Importantly, inhibiting the kinase activation of NIK by the small molecule B022 prevents NIK- or H2O2-induced β cell death and also reduces streptozotocin (STZ)-induced β cell death while ameliorating hyperglycemia, suggesting that the kinase activity of NIK is essential in inducing islet inflammation, β cell death, and diabetes. In all, this study not only uncovers a role of NIK in β cell failure but also provides a potential therapeutic target for the treatment of diabetes.

Keywords

NF-κB-inducing kinase; diabetes; inflammation; insulin secretion; islet β cells.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z