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他汀类药物引起新发糖尿病风险升高的病理机制:LDLR介导胆固醇内流引起胰岛β细胞“脂毒性” 被引量:1

Pathomechanism of statins induced increased risk of new onset diabetes: LDLR mediated cholesterol influx induces lipid toxicity in pancreatic β cells
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摘要 高血脂是心血管病与糖尿病的共同危险因素,然而临床上使用他汀类药物控制血脂却增加了患者新发糖尿病的风险。相反,家族性高胆固醇血症(FH)病人有较高的血脂并长期使用他汀类药物,这类患者罹患糖尿病的风险却降低了。考虑到FH病人主要是由低密度脂蛋白受体(LDLR)突变引起的,这使得LDLR介导的胆固醇代谢是否参与糖尿病的发病成为疑问。他汀类药物能够上调肝脏和某些组织的LDLR表达并促进胆固醇内流,有可能引起某些胰岛细胞"脂毒性"的发生。胰岛β细胞对胆固醇较敏感,少量胆固醇蓄积就能造成细胞功能障碍。本文旨在讨论LDLR在他汀类药物诱发的糖尿病中的病理角色,为降低该药的不良反应、促进2型糖尿病的防治提供新的思考。 Hyperlipidemia is a common risk factor for cardiovascular disease and diabetes. However,the clinical use of statins to control blood lipids increases the risk of new onset diabetes in patients. Conversely,patients with familial hypercholesterolemia( FH) have higher blood lipids and long-term use of statins,which reduce the risk of diabetes. Considering that FH patient is mainly caused by low density lipoprotein receptor( LDLR) mutation,this makes it possible for LDLR mediated cholesterol metabolism to be involved in the onset of diabetes. Statins can upregulate LDLR expression in liver and some tissues and promote cholesterol influx,which may cause some lipotoxicity in some pancreatic islet cells.Pancreatic β cells are more sensitive to cholesterol,and a small amount of cholesterol accumulation can cause cell dysfunction. The purpose of this paper is to discuss the pathological role of LDLR in statins induced diabetes,and to provide new thinking for reducing the adverse reaction of statins and promoting the prevention and treatment of type 2 diabetes.
作者 余琦 王章利 张光伟 徐仓宝 YU Qi1,2, WANG Zhang-Li1, ZHANG Guang-Wei1 , XU Cang-Bao1 (1.Key Laboratory of lschemic Cardiovascular Disease in Shaanxi & Institute of Basic and Translational Medicine of Xi'an Medical University, Xi'an, Shaanxi 710021, China ; 2.Department of Histology and Embryology, Xi'an Medical University, Xi'an , Shaanxi 710021, China)
出处 《中国动脉硬化杂志》 2018年第4期342-346,共5页 Chinese Journal of Arteriosclerosis
基金 国家自然科学基金(81400328、81773795) 陕西省自然科学基础研究计划面上项目(2016JM8025) 陕西省教育厅专项科研计划项目(17JS116)
关键词 他汀类药物 糖尿病 低密度脂蛋白受体 胆固醇内流 Statins Diabetes mellitus Low density lipoprotein receptor Cholesterol influx
作者简介 余琦,博士,副教授,研究方向为动脉粥样硬化病理机制及脂代谢异常,E-mail为qiyu6028@hotmail.com。;通讯作者 徐仓宝,博士,教授,研究方向为心血管病及血管功能,E-mail为cangbaoxu@yahoo.com。
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