Secretory autophagy promotes RAB37-mediated insulin secretion under glucose stimulation both in vitro and in vivo

Shan Ying Wu, Hung Tsung Wu, Yi Ching Wang, Chih Jen Chang, Yan Shen Shan, Shang Rung Wu, Yen Chi Chiu, Chia Lang Hsu, Hsueh Fen Juan, Kai Ying Lan, Chi Wen Chu, Ying Ray Lee, Sheng Hui Lan, Hsiao Sheng Liu

研究成果: Article同行評審

6 引文 斯高帕斯(Scopus)

摘要

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.

原文English
頁(從 - 到)1239-1257
頁數19
期刊Autophagy
19
發行號4
DOIs
出版狀態Published - 2023

All Science Journal Classification (ASJC) codes

  • 分子生物學
  • 細胞生物學

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