RILP Restricts Insulin Secretion Through Mediating Lysosomal Degradation of Proinsulin

RILP Restricts Insulin Secretion Through Mediating Lysosomal Degradation of Proinsulin
Title:
RILP Restricts Insulin Secretion Through Mediating Lysosomal Degradation of Proinsulin
Other Titles:
Diabetes
Keywords:
Publication Date:
17 October 2019
Citation:
RILP Restricts Insulin Secretion Through Mediating Lysosomal Degradation of Proinsulin Yuxia Zhou, Zhiyu Liu, Shengmei Zhang, Ruijuan Zhuang, Huiying Liu, Xiaoqing Liu, Xi Qiu, Ming Zhang, Yanpan Zheng, Liangcheng Li, Wanjin Hong, Tuanlao Wang Diabetes Jan 2020, 69 (1) 67-82; DOI: 10.2337/db19-0086
Abstract:
Insulin secretion is tightly regulated by membrane trafficking. RILP (Rab7 interacting lysosomal protein) regulates the endocytic trafficking, but its role in insulin secretion has not been investigated. In this study, we found that overexpression of RILP inhibited insulin secretion in both the β-cell lines and freshly isolated islets. Consequently, the expression of RILP in islets suppressed the ability to recover the glucose homeostasis in type 1 diabetes mice upon transplantation. Of physiological relevance is that RILP expression was upregulated in the diabetic mouse islets. Mechanistically, overexpression of RILP induced insulin granule clustering, decreased the number of proinsulin-containing granules in β-cells, and significantly promoted proinsulin degradation. Conversely, RILP depletion sustained proinsulin and increased insulin secretion. The proinsulin degradation induced by RILP expression was inhibited by lysosomal inhibitors and was Rab7-dependent. Finally, we showed that RILP interacts with insulin granule–associated Rab26 to restrict insulin secretion. This study presents a new pathway regulating insulin secretion and mechanically demonstrates a novel function of RILP in modulating insulin secretion through mediating the lysosomal degradation of proinsulin.
License type:
PublisherCopyrights
Funding Info:
This work was supported by National Natural Science Foundation of China (No.31671478 and No.31871423). We are grateful to Prof. Tao Xu to provide us INS-1 cells (College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China).
Description:
ISSN:
0012-1797
1939-327X
Files uploaded:

File Size Format Action
db19-0086.pdf 4.19 MB PDF Open