Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: A mechanism for the action of berberine to activate AMP-Activated protein kinase and improve insulin action

doi:10.2337/db07-1552

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	Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: A mechanism for the action of berberine to activate AMP-Activated protein kinase and improve insulin action
	Turner, Nigel 1; Li, Jing-Ya1,2 ; Gosby, Alison 1; To, Sabrina W. C.1; Cheng, Zhe 2; Miyoshi, Hiroyuki 3; Taketo, Makoto M.3; Cooney, Gregory J.1; Kraegen, Edward W.1; James, David E.1
刊名	DIABETES
	2008-05
卷号	57 期号:5 页码:1414-1418
ISSN号	0012-1797
DOI	10.2337/db07-1552
文献子类	Article
英文摘要	OBJECTIVE-Berberine (BBR) activates AMP-activated protein kinase (AMPK) and improves insulin sensitivity in rodent models of insulin resistance. We investigated the mechanism of activation of AMPK by BBR and explored whether derivatization of BBR could improve its in vivo efficacy. RESEARCH DESIGN AND METHODS-AMPK phosphorylation was examined in L6 myotubes and LYB1(-/-) cells, with or without the Ca2(+)/calmodulin-dependent protein kinase kinase (CAMKK) inhibitor STO-609. Oxygen consumption was measured in L6 myotubes and isolated muscle mitochondria. The effect of a BBR derivative, dihydroberberine (dhBBR), on adiposity and glucose metabolism was examined in rodents fed a high-fat diet. RESULTS-We have made the following novel observations: 1) BBR dose-dependently inhibited respiration in L6 myotubes and muscle mitochondria, through a specific effect on respiratory complex 1, similar to that observed with metforn-tin and rosiglitazone; 2) activation of AMPK by BBR did not rely on the activity of either LKB1 or CAMKK beta, consistent with major regulation at the level of the AMPK phosphatase; and 3) a novel BBR derivative, dhBBR, was identified that displayed improved in vivo efficacy in terms of counteracting increased adiposity, tissue triglyceride accumulation, and insulin resistance in high-fat-fed rodents. This effect is likely due to enhanced oral bioavailability. CONCLUSIONS-Complex I of the respiratory chain represents a major target for compounds that improve whole-body insulin sensitivity through increased AMPK activity. The identification of a novel derivative of BBR with improved in vivo efficacy highlights the potential importance of BBR as a novel therapy for the treatment of type 2 diabetes.
WOS关键词	METFORMIN ; CHAIN ; METABOLISM ; LIVER
WOS研究方向	Endocrinology & Metabolism
语种	英语
出版者	AMER DIABETES ASSOC
WOS记录号	WOS:000255628700034
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272926]
专题	国家新药筛选中心药物安全性评价中心
通讯作者	Ye, Ji-Ming
作者单位	1.Garvan Inst Med Res, Diabet & Obes Res Program, Sydney, NSW 2010, Australia; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China; 3.Kyoto Univ, Dept Pharmacol, Grad Sch Med, Kyoto, Japan
推荐引用方式 GB/T 7714	Turner, Nigel,Li, Jing-Ya,Gosby, Alison,et al. Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: A mechanism for the action of berberine to activate AMP-Activated protein kinase and improve insulin action[J]. DIABETES,2008,57(5):1414-1418.
APA	Turner, Nigel.,Li, Jing-Ya.,Gosby, Alison.,To, Sabrina W. C..,Cheng, Zhe.,...&Ye, Ji-Ming.(2008).Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: A mechanism for the action of berberine to activate AMP-Activated protein kinase and improve insulin action.DIABETES,57(5),1414-1418.
MLA	Turner, Nigel,et al."Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: A mechanism for the action of berberine to activate AMP-Activated protein kinase and improve insulin action".DIABETES 57.5(2008):1414-1418.