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学科主题临床医学
Mechanisms of metformin inhibiting lipolytic response to isoproterenol in primary rat adipocytes
Zhang, Tingting1,2; He, Jinhan1; Xu, Chong1; Zu, Luxia1; Jiang, Hongfeng1; Pu, Shenshen1; Guo, Xiaohui2; Xu, Guoheng1
刊名JOURNAL OF MOLECULAR ENDOCRINOLOGY
2009
DOI10.1677/JME-08-0130
42期:1-2页:57-66
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Endocrinology & Metabolism
研究领域[WOS]Endocrinology & Metabolism
关键词[WOS]HORMONE-SENSITIVE LIPASE ; ACTIVATED PROTEIN-KINASE ; ADIPOSE TRIGLYCERIDE LIPASE ; NECROSIS-FACTOR-ALPHA ; LIPID-METABOLISM ; STIMULATED LIPOLYSIS ; GLUCOSE-PRODUCTION ; DIABETES-MELLITUS ; PERILIPIN-A ; TISSUE
英文摘要

The mobilization of free fatty acids (FFA) from adipose tissue to the bloodstream primarily depends on triacylglycerol lipolysis in adipocytes. Catecholamines are major hormones that govern lipolysis through elevating cellular CAMP production and activating protein kinase, CAMP dependent, catalytic, alpha (PKA) and mitogen-activated protein kinase 1/2 (MAPK1/3). Obesity and type 2 diabetes are associated with elevated levels of systemic FFA, which restricts glucose utilization and induces insulin resistance. The biguanide metformin exerts its antihyperglycemic effect by enhancing insulin sensitivity, which is associated with decreased levels of circulating FFA. In this study, we examined the characteristics and basis of the inhibitory effect of metformin on adrenergic-stimulated lipolysis in primary rat adipocytes. We measured the release of FFA and glycerol as an index of lipolysis and examined the major signalings of the lipolytic cascade in primary rat adipocytes. Metformin at 250-500 mu M efficiently attenuated FFA and glycerol release from the adipocytes stimulated with 1 mu M isoproterenol. To elucidate the basis for this antilipolytic action, we showed that metformin decreased cellular CAMP production, reduced the activities of PKA and MAPK1/3, and attenuated the phosphorylation of perilipin during isoproterenol-stimulated lipolysis. Further, metformin suppressed isoproterenol-promoted lipase activity but did not affect the translocation of lipase, hormone-sensitive from the cytosol to lipid droplets in adipocytes. This study provides evidence that metformin acts on adipocytes to suppress the lipolysis response to catecholamine. This antilipolytic effect could be a cellular basis for metformin decreasing plasma FFA levels and improving insulin sensitivity.

语种英语
WOS记录号WOS:000263362900006
项目编号2009CB941603 ; 2006CB503903 ; 30890042 ; 30770803 ; 30670779 ; 5072030
资助机构National basic Research Program of China ; National Natural Science Foundation of China ; Beijing Natural Science Foundation
引用统计
被引频次:32[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/54620
专题北京大学第一临床医学院_内分泌内科
北京大学基础医学院
作者单位1.Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100191, Peoples R China
2.Peking Univ, Hosp 1, Dept Endocrinol, Beijing 100034, Peoples R China
推荐引用方式
GB/T 7714
Zhang, Tingting,He, Jinhan,Xu, Chong,et al. Mechanisms of metformin inhibiting lipolytic response to isoproterenol in primary rat adipocytes[J]. JOURNAL OF MOLECULAR ENDOCRINOLOGY,2009,42(1-2):57-66.
APA Zhang, Tingting.,He, Jinhan.,Xu, Chong.,Zu, Luxia.,Jiang, Hongfeng.,...&Xu, Guoheng.(2009).Mechanisms of metformin inhibiting lipolytic response to isoproterenol in primary rat adipocytes.JOURNAL OF MOLECULAR ENDOCRINOLOGY,42(1-2),57-66.
MLA Zhang, Tingting,et al."Mechanisms of metformin inhibiting lipolytic response to isoproterenol in primary rat adipocytes".JOURNAL OF MOLECULAR ENDOCRINOLOGY 42.1-2(2009):57-66.
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