Secretory autophagy promotes RAB37-mediated insulin secretion under glucose stimulation both in vitro and in vivo
Journal
Autophagy
Pages
1-19
Date Issued
2022-09-15
Author(s)
Wu, Shan-Ying
Wu, Hung-Tsung
Wang, Yi-Ching
Chang, Chih-Jen
Shan, Yan-Shen
Wu, Shang-Rung
Chiu, Yen-Chi
Hsu, Chia-Lang
Lan, Kai-Ying
Chu, Chi-Wen
Lee, Ying-Ray
Lan, Sheng-Hui
Liu, Hsiao-Sheng
Abstract
High blood glucose is one of the risk factors for metabolic disease and INS (insulin) is the key regulatory hormone for glucose homeostasis. Hypoinsulinemia accompanied with hyperglycemia was diagnosed in mice with pancreatic β-cells exhibiting autophagy deficiency; however, the underlying mechanism remains elusive. The role of secretory autophagy in the regulation of metabolic syndrome is gaining more attention. Our data demonstrated that increased macroautophagic/autophagic activity leads to induction of insulin secretion in β-cells both in vivo and in vitro under high-glucose conditions. Moreover, proteomic analysis of purified autophagosomes from β-cells identified a group of vesicular transport proteins participating in insulin secretion, implying that secretory autophagy regulates insulin exocytosis. RAB37, a small GTPase, regulates vesicle biogenesis, trafficking, and cargo release. We demonstrated that the active form of RAB37 increased MAP1LC3/LC3 lipidation (LC3-II) and is essential for the promotion of insulin secretion by autophagy, but these phenomena were not observed in rab37 knockout (rab37-/-) cells and mice. Unbalanced insulin and glucose concentration in the blood was improved by manipulating autophagic activity using a novel autophagy inducer niclosamide (an antihelminthic drug) in a high-fat diet (HFD)-obesity mouse model. In summary, we reveal that secretory autophagy promotes RAB37-mediated insulin secretion to maintain the homeostasis of insulin and glucose both in vitro and in vivo.
Subjects
Glucose-stimulated insulin secretion; LC3; RAB37; insulin; secretory autophagy
SDGs
Publisher
TAYLOR & FRANCIS INC
Type
journal article