@article{0f62727b10fa4c4ead616a8ff553461e,
title = "Secretory autophagy promotes RAB37-mediated insulin secretion under glucose stimulation both in vitro and in vivo",
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.",
keywords = "Glucose-stimulated insulin secretion, insulin, LC3, RAB37, secretory autophagy",
author = "Wu, {Shan Ying} and Wu, {Hung Tsung} and Wang, {Yi Ching} and Chang, {Chih Jen} and Shan, {Yan Shen} and Wu, {Shang Rung} and Chiu, {Yen Chi} and Hsu, {Chia Lang} and Juan, {Hsueh Fen} and Lan, {Kai Ying} and Chu, {Chi Wen} and Lee, {Ying Ray} and Lan, {Sheng Hui} and Liu, {Hsiao Sheng}",
note = "Funding Information: We thank Dr. Thomas Melia (Yale University, USA) for providing the in vitro system for the LC3 and GL1 lipidation reactions. We thank the technical services provided by the “Transgenic Mouse Model Core Facility of the National Core Facility Program for Biotechnology, Ministry of Science and Technology, Taiwan” and the “Gene Knockout Mouse Core Laboratory of National Taiwan University Center of Genomic Medicine”. This work was financially supported by the Cancer Progression Research Center of National Yang Ming Chiao Tung University, which runs the Featured Areas Research Center Program within the framework of the Higher Education Sprout Project (Ministry of Education, Taiwan), Ministry of Science and Technology (MOST 109-2320-B-010-020 and MOST 109-2314-B-038-119-MY2), Taipei, Taiwan, and Kaohsiung Medical University Research Center (KMUTC108A04-0 and KMU-TC108A04-2), Kaohsiung, Taiwan. Taipei Medical University (TMU108-AE1-B39), Taipei, Taiwan. Publisher Copyright: {\textcopyright} 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.",
year = "2022",
doi = "10.1080/15548627.2022.2123098",
language = "English",
volume = "19",
pages = "1239--1257",
journal = "Autophagy",
issn = "1554-8627",
publisher = "Landes Bioscience",
number = "4",
}