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线粒体底物偏好性的改变并不会造成肌肉胰岛素抵抗
作者:小柯机器人 发布时间:2020/10/10 14:02:15

美国耶鲁大学医学院Gerald I. Shulman和Kitt Falk Petersen研究团队合作揭示,线粒体底物偏好性改变并不是肌肉胰岛素抵抗的必要条件。2020年10月8日,国际学术期刊《细胞-代谢》在线发表了这一成果。

为了揭示肌肉线粒体底物偏好性改变在肌肉胰岛素抵抗中的作用,研究人员评估了线粒体丙酮酸氧化(VPDH)与肌肉中线粒体柠檬酸合酶通量(VCS)的比率。与之前的认知相反,研究发现喂养高脂饮食(HFD)的胰岛素抵抗大鼠在空腹状态下其比目鱼肌或股四头肌中并未表现出肌肉底物偏好性(VPDH/VCS)的改变。

此外,高胰岛素-正常血糖(HE)检测表明在正常和胰岛素抵抗大鼠的肌肉中均增加了VPDH/VCS。随后,通过检测胰岛素敏感和胰岛素抵抗人群肌肉中VPDH / VCS的通量,研究人员发现过夜禁食后(约20%)他们具有相似的VPDH / VCS相对比率,HE检测期间VPDH/VCS通量的增加也相似。总而言之,这些发现表明,线粒体底物偏好性的改变并不是肌肉胰岛素抵抗发病的必要条件。

据了解,肌肉线粒体底物偏好性的改变被认为是引起肌肉胰岛素抵抗的主要作用原因。

附:英文原文

Title: Dissociation of Muscle Insulin Resistance from Alterations in Mitochondrial Substrate Preference

Author: Joongyu D. Song, Tiago C. Alves, Douglas E. Befroy, Rachel J. Perry, Graeme F. Mason, Xian-Man Zhang, Alexander Munk, Ye Zhang, Dongyan Zhang, Gary W. Cline, Douglas L. Rothman, Kitt Falk Petersen, Gerald I. Shulman

Issue&Volume: 2020-10-08

Abstract: Alterations in muscle mitochondrial substrate preference have been postulated to playa major role in the pathogenesis of muscle insulin resistance. In order to examinethis hypothesis, we assessed the ratio of mitochondrial pyruvate oxidation (VPDH) to rates of mitochondrial citrate synthase flux (VCS) in muscle. Contrary to this hypothesis, we found that high-fat-diet (HFD)-fed insulin-resistantrats did not manifest altered muscle substrate preference (VPDH/VCS) in soleus or quadriceps muscles in the fasting state. Furthermore, hyperinsulinemic-euglycemic(HE) clamps increased VPDH/VCS in both muscles in normal and insulin-resistant rats. We then examined the muscleVPDH/VCS flux in insulin-sensitive and insulin-resistant humans and found similar relativerates of VPDH/VCS, following an overnight fast (~20%), and similar increases in VPDH/VCS fluxes during a HE clamp. Altogether, these findings demonstrate that alterationsin mitochondrial substrate preference are not an essential step in the pathogenesisof muscle insulin resistance.

DOI: 10.1016/j.cmet.2020.09.008

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30486-1

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:22.415
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx