小柯机器人

美国圣路易斯华盛顿大学Clay F. Semenkovich等研究人员合作发现，棕榈酰化连接糖尿病患者的胰岛素过度分泌和β细胞衰竭。这一研究成果于2023年1月11日在线发表在国际学术期刊《细胞—代谢》上。

研究人员表示，高胰岛素血症往往出现在2型糖尿病之前。牵涉胞吐的棕榈酰化，被APT1逆转。APT1的生物学特性在2型糖尿病患者的胰腺中发生了改变，APT1在非糖尿病患者的胰腺中被敲低，导致胰岛素分泌过剩。APT1基因敲除的小鼠的胰岛自主增加了葡萄糖刺激的胰岛素分泌，这与胰岛素颗粒融合的时间延长有关。

附：英文原文

Title: Palmitoylation couples insulin hypersecretion with β cell failure in diabetes

Author: Guifang Dong, Sangeeta Adak, George Spyropoulos, Qiang Zhang, Chu Feng, Li Yin, Sarah L. Speck, Zeenat Shyr, Shuntaro Morikawa, Rie Asada Kitamura, Rahul S. Kathayat, Bryan C. Dickinson, Xue Wen Ng, David W. Piston, Fumihiko Urano, Maria S. Remedi, Xiaochao Wei, Clay F. Semenkovich

Issue&Volume: 2023-01-11

Abstract: Hyperinsulinemia often precedes type 2 diabetes. Palmitoylation, implicated in exocytosis,is reversed by acyl-protein thioesterase 1 (APT1). APT1 biology was altered in pancreaticislets from humans with type 2 diabetes, and APT1 knockdown in nondiabetic isletscaused insulin hypersecretion. APT1 knockout mice had islet autonomous increased glucose-stimulatedinsulin secretion that was associated with prolonged insulin granule fusion. Usingpalmitoylation proteomics, we identified Scamp1 as an APT1 substrate that localizedto insulin secretory granules. Scamp1 knockdown caused insulin hypersecretion. Expressionof a mutated Scamp1 incapable of being palmitoylated in APT1-deficient cells rescuedinsulin hypersecretion and nutrient-induced apoptosis. High-fat-fed islet-specificAPT1-knockout mice and global APT1-deficient db/db mice showed increased β cell failure. These findings suggest that APT1 is regulatedin human islets and that APT1 deficiency causes insulin hypersecretion leading toβ cell failure, modeling the evolution of some forms of human type 2 diabetes.

DOI: 10.1016/j.cmet.2022.12.012

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00549-6

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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