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http://libir.tmu.edu.tw/handle/987654321/65176
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題名: | Secretory autophagy promotes RAB37-mediated insulin secretion under glucose stimulation both in vitro and in vivo |
作者: | 吳珊瑩 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 |
貢獻者: | 醫學系微生物免疫學科 |
日期: | 2022-09 |
上傳時間: | 2025-03-27 11:44:45 (UTC+8) |
摘要: | 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. |
關聯: | Autophagy, 19(4), 1239–1257 |
描述: | 【112-1 升等】臺北醫學大學教師升等專門著作 職別:專任 送審等級:副教授 著作送審 |
資料類型: | article |
顯示於類別: | [教師升等送審著作] 112 [微生物免疫學科] 期刊論文
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