突变亨廷顿蛋白对葡萄糖代谢的影响及其机制  

Effect of mutant huntingtin on glucose metabolism and its mechanism

作　　者：孙云[1] 李臻[2] 丁丹丹 曹玉洁 秦婉 张琪 叶翠芳[1] 

机构地区：[1]华中科技大学同济医学院基础医学院组织胚胎学教研室 [2]华中科技大学同济医学院

出　　处：《中国组织化学与细胞化学杂志》2015年第5期484-488,共5页Chinese Journal of Histochemistry and Cytochemistry

基　　金：华中科技大学创新创业训练计划项目(13B339);华中科技大学国家级大学生创新创业训练计划项目(201410487058)

摘　　要：亨廷顿病(Huntington’s disease,HD)是一种常染色体显性遗传性的神经退行性疾病,主要累及中老年人群。HD患者除了表现出运动失调、认知异常、体重减轻外,还有明显的葡萄糖糖代谢异常,甚至发生糖尿病。本文综述了HD葡萄糖代谢紊乱及其机制的研究现状。突变的亨廷顿蛋白(huntingtin,Htt)在神经元和外周组织如胰岛内广泛表达,并对细胞造成毒性损伤。突变Htt诱发葡萄糖代谢异常和糖尿病的机制尚不明确。以往的研究已经证实突变Htt可能通过多个机制损伤胰岛β细胞功能:胰岛素分泌小泡数减少,胰岛素基因表达降低,胰岛素分泌的抑制和线粒体功能损伤所致的系统能量稳态失衡。其中线粒体损伤和能量代谢异常是多种神经退行性疾病和II型糖尿病共有的发病机制。Huntington’s disease( HD) is an autosomal dominant neurodegenerative disease,affecting mainly the middle-aged and old population. HD patients have choreatic movements,dementia and weight loss. Further,they show disturbance of glucose metabolism and even have diabetes mellitus. This article reviews glucose metabolic disturbance and its mechanism in HD. Mutant huntingtin( Htt) is widely distributed in neurons and peripheral tissues such as pancreatic islets,and causes cytotoxicity. The mechanism of glucose metabolic disturbance and diabetes mellitus caused by mutant Htt is still unknown. Mutant Htt has been proved to impair pancreatic cells by several mechanisms: reduced number of insulin-containing secretory vesicles,decreased insulin gene expression,inhibition of insulin secretion,and imbalance of systemic energy homeostasis caused by mitochondria impairment. The last two are considered the common pathogenesis of several neurodegenerative diseases and type II diabetes mellitus.

关 键 词：亨廷顿病 亨廷顿蛋白 糖尿病 血糖 胰岛素 

分 类 号：R587.1[医药卫生—内分泌]