Arctigenin, a natural compound, activates AMP-activated protein kinase via inhibition of mitochondria complex I and ameliorates metabolic disorders in ob/ob mice

doi:10.1007/s00125-011-2366-3

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	Arctigenin, a natural compound, activates AMP-activated protein kinase via inhibition of mitochondria complex I and ameliorates metabolic disorders in ob/ob mice
	Huang, S. -L.1; Yu, R. -T.2; Gong, J.1; Feng, Y.1; Dai, Y. -L.1; Hu, F.1; Hu, Y. -H.1; Tao, Y. -D.2; Leng, Y.1
刊名	DIABETOLOGIA
	2012-05
卷号	55 期号:5 页码:1469-1481
关键词	AMP-activated protein kinase Gluconeogenesis Glucose uptake Lipid synthesis Mitochondria Natural compound Respiratory complex I
ISSN号	0012-186X
DOI	10.1007/s00125-011-2366-3
文献子类	Article
英文摘要	Aims/hypothesis Arctigenin is a natural compound that had never been previously demonstrated to have a glucose-lowering effect. Here it was found to activate AMP-activated protein kinase (AMPK), and the mechanism by which this occurred, as well as the effects on glucose and lipid metabolism were investigated. Methods 2-Deoxyglucose uptake and AMPK phosphorylation were examined in L6 myotubes and isolated skeletal muscle. Gluconeogenesis and lipid synthesis were evaluated in rat primary hepatocytes. The acute and chronic effects of arctigenin on metabolic abnormalities were observed in C57BL/6J and ob/ob mice. Changes in mitochondrial membrane potential were measured using the J-aggregate-forming dye, JC-1. Analysis of respiration of L6 myotubes or isolated mitochondria was conducted in a channel oxygen system. Results Arctigenin increased AMPK phosphorylation and stimulated glucose uptake in L6 myotubes and isolated skeletal muscles. In primary hepatocytes, it decreased gluconeogenesis and lipid synthesis. The enhancement of glucose uptake and suppression of hepatic gluconeogenesis and lipid synthesis by arctigenin were prevented by blockade of AMPK activation. The respiration of L6 myotubes or isolated mitochondria was inhibited by arctigenin with a specific effect on respiratory complex I. A single oral dose of arctigenin reduced gluconeogenesis in C57BL/6J mice. Chronic oral administration of arctigenin lowered blood glucose and improved lipid metabolism in ob/ob mice. Conclusions/interpretation This study demonstrates a new role for arctigenin as a potent indirect activator of AMPK via inhibition of respiratory complex I, with beneficial effects on metabolic disorders in ob/ob mice. This highlights the potential value of arctigenin as a possible treatment of type 2 diabetes.
资助项目	National Basic Research Program of China (973 Program)[2009CB522300] ; National Nature Science Foundation of China[90813029]
WOS关键词	SKELETAL-MUSCLE ; INSULIN-RESISTANCE ; GLUCOSE-TRANSPORT ; METFORMIN ; CELLS ; MECHANISM ; EXERCISE ; STRESS ; IDENTIFICATION ; BERBERINE
WOS研究方向	Endocrinology & Metabolism
语种	英语
出版者	SPRINGER
WOS记录号	WOS:000302994600030
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278101]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Leng, Y.
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, NW Plateau Biol Inst, Xining 810008, Peoples R China
推荐引用方式 GB/T 7714	Huang, S. -L.,Yu, R. -T.,Gong, J.,et al. Arctigenin, a natural compound, activates AMP-activated protein kinase via inhibition of mitochondria complex I and ameliorates metabolic disorders in ob/ob mice[J]. DIABETOLOGIA,2012,55(5):1469-1481.
APA	Huang, S. -L..,Yu, R. -T..,Gong, J..,Feng, Y..,Dai, Y. -L..,...&Leng, Y..(2012).Arctigenin, a natural compound, activates AMP-activated protein kinase via inhibition of mitochondria complex I and ameliorates metabolic disorders in ob/ob mice.DIABETOLOGIA,55(5),1469-1481.
MLA	Huang, S. -L.,et al."Arctigenin, a natural compound, activates AMP-activated protein kinase via inhibition of mitochondria complex I and ameliorates metabolic disorders in ob/ob mice".DIABETOLOGIA 55.5(2012):1469-1481.