DW14006 as a Direct AMPK alpha Activator Ameliorates Diabetic Peripheral Neuropathy in Mice

doi:10.2337/db19-1084

	DW14006 as a Direct AMPK alpha Activator Ameliorates Diabetic Peripheral Neuropathy in Mice
	Xu, Xu 1; Wang, Wei 2,3; Wang, Zhengyu 4; Lv, Jianlu 1; Xu, Xiaoju 1; Xu, Jiawen 1; Yang, Juanzhen 1; Zhu, Xialin 1; Lu, Yin 1; Duan, Wenhu 2,3
刊名	DIABETES
	2020-09-01
卷号	69 期号:9 页码:1974-1988
ISSN号	0012-1797
DOI	10.2337/db19-1084
通讯作者	Wang, Jiaying(wangjy@njucm.edu.cn) ; Zhou, Jinpei(zhjp@cpu.edu.cn) ; Shen, Xu(xshen@njucm.edu.cn)
英文摘要	Diabetic peripheral neuropathy (DPN) is a long-term complication of diabetes with a complicated pathogenesis. AMP-activated protein kinase (AMPK) senses oxidative stress, and mitochondrial function plays a central role in the regulation of DPN. Here, we reported that DW14006 (2-[3-(7-chloro-6-[2 '-hydroxy-(1,1 '-biphenyl)-4-yl]-2-oxo-1,2-dihydroquinolin-3-yl)phenyl]acetic acid) as a direct AMPK alpha activator efficiently ameliorated DPN in both streptozotocin (STZ)-induced type 1 and BKSdb/dbtype 2 diabetic mice. DW14006 administration highly enhanced neurite outgrowth of dorsal root ganglion neurons and improved neurological function in diabetic mice. The underlying mechanisms have been intensively investigated. DW14006 treatment improved mitochondrial bioenergetics profiles and restrained oxidative stress and inflammation in diabetic mice by targeting AMPK alpha, which has been verified by assay against the STZ-induced diabetic mice injected with adeno-associated virus 8-AMPK alpha-RNAi. To our knowledge, our work might be the first report on the amelioration of the direct AMPK alpha activator on DPN by counteracting multiple risk factors including mitochondrial dysfunction, oxidative stress, and inflammation, and DW14006 has been highlighted as a potential leading compound in the treatment of DPN.
资助项目	National Science & Technology Major Project Key New Drug Creation and Manufacturing Program of China[2018ZX09711002] ; National Natural Science Foundation for Young Scientists of China[81703806] ; Postgraduate Research & Practice Innovation Program of Jiangsu Province[KYCX18_1600] ; Open Project Program of Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica[JKLPSE201801] ; Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions(Integration of Chinese and Western Medicine)
WOS关键词	ROOT GANGLIA NEURONS ; MITOCHONDRIAL DYSFUNCTION ; OXIDATIVE STRESS ; KINASE ; MECHANISMS ; BIOENERGETICS ; PATHOGENESIS ; ALLODYNIA ; GLUCOSE ; TARGET
WOS研究方向	Endocrinology & Metabolism
语种	英语
出版者	AMER DIABETES ASSOC
WOS记录号	WOS:000560863400013
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/292339]
专题	中国科学院上海药物研究所
通讯作者	Wang, Jiaying; Zhou, Jinpei; Shen, Xu
作者单位	1.Nanjing Univ Chinese Med, Jiangsu Key Lab Pharmacol & Safety Evaluat Chines, Nanjing, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Medica, Dept Med Chem, Shanghai, Peoples R China 3.Univ Chinese Acad Sci, Beijing, Peoples R China 4.China Pharmaceut Univ, Dept Med Chem, Nanjing, Peoples R China
推荐引用方式 GB/T 7714	Xu, Xu,Wang, Wei,Wang, Zhengyu,et al. DW14006 as a Direct AMPK alpha Activator Ameliorates Diabetic Peripheral Neuropathy in Mice[J]. DIABETES,2020,69(9):1974-1988.
APA	Xu, Xu.,Wang, Wei.,Wang, Zhengyu.,Lv, Jianlu.,Xu, Xiaoju.,...&Shen, Xu.(2020).DW14006 as a Direct AMPK alpha Activator Ameliorates Diabetic Peripheral Neuropathy in Mice.DIABETES,69(9),1974-1988.
MLA	Xu, Xu,et al."DW14006 as a Direct AMPK alpha Activator Ameliorates Diabetic Peripheral Neuropathy in Mice".DIABETES 69.9(2020):1974-1988.