Activation of AMPK by Bitter Melon Triterpenoids Involves CaMKK beta

doi:10.1371/journal.pone.0062309

	Activation of AMPK by Bitter Melon Triterpenoids Involves CaMKK beta
	Iseli, Tristan J.2; Turner, Nigel 2; Zeng, Xiao-Yi 1,2,3; Cooney, Gregory J.2; Kraegen, Edward W.2; Yao, Sheng4 ; Ye, Yang4 ; James, David E.2; Ye, Ji-Ming 1,2,3,4
刊名	PLOS ONE
	2013-04-25
卷号	8 期号:4
ISSN号	1932-6203
DOI	10.1371/journal.pone.0062309
文献子类	Article
英文摘要	We recently showed that bitter melon-derived triterpenoids (BMTs) activate AMPK and increase GLUT4 translocation to the plasma membrane in vitro, and improve glucose disposal in insulin resistant models in vivo. Here we interrogated the mechanism by which these novel compounds activate AMPK, a leading anti-diabetic drug target. BMTs did not activate AMPK directly in an allosteric manner as AMP or the Abbott compound (A-769662) does, nor did they activate AMPK by inhibiting cellular respiration like many commonly used anti-diabetic medications. BMTs increased AMPK activity in both L6 myotubes and LKB1-deficient HeLa cells by 20-35%. Incubation with the CaMKK beta inhibitor, STO-609, completely attenuated this effect suggesting a key role for CaMKK beta in this activation. Incubation of L6 myotubes with the calcium chelator EGTA-AM did not alter this activation suggesting that the BMT-dependent activation was Ca2+-independent. We therefore propose that CaMKK beta is a key upstream kinase for BMT-induced activation of AMPK.
资助项目	National Health and Medical Research Council of Australia (NHMRC)[535930] ; Australia-China Special Fund[CH0812110]
WOS关键词	KINASE KINASE-BETA ; DEPENDENT PROTEIN-KINASE ; MOMORDICA-CHARANTIA ; METABOLIC SYNDROME ; COMPLEX ; BERBERINE ; MECHANISM ; RECEPTOR ; IDENTIFICATION ; LOCALIZATION
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000318341400049
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277647]
专题	中国科学院上海药物研究所
通讯作者	Ye, Ji-Ming
作者单位	1.RMIT Univ, Sch Hlth Sci, Melbourne, Vic, Australia; 2.Garvan Inst Med Res, Diabet & Obes Res Program, Sydney, NSW, Australia; 3.RMIT Univ, Hlth Innovat Res Inst, Melbourne, Vic, Australia; 4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China
推荐引用方式 GB/T 7714	Iseli, Tristan J.,Turner, Nigel,Zeng, Xiao-Yi,et al. Activation of AMPK by Bitter Melon Triterpenoids Involves CaMKK beta[J]. PLOS ONE,2013,8(4).
APA	Iseli, Tristan J..,Turner, Nigel.,Zeng, Xiao-Yi.,Cooney, Gregory J..,Kraegen, Edward W..,...&Ye, Ji-Ming.(2013).Activation of AMPK by Bitter Melon Triterpenoids Involves CaMKK beta.PLOS ONE,8(4).
MLA	Iseli, Tristan J.,et al."Activation of AMPK by Bitter Melon Triterpenoids Involves CaMKK beta".PLOS ONE 8.4(2013).