RT Journal Article SR Electronic T1 DW14006 as a Direct AMPKα Activator Ameliorates Diabetic Peripheral Neuropathy in Mice JF Diabetes JO Diabetes FD American Diabetes Association SP 1974 OP 1988 DO 10.2337/db19-1084 VO 69 IS 9 A1 Xu, Xu A1 Wang, Wei A1 Wang, Zhengyu A1 Lv, Jianlu A1 Xu, Xiaoju A1 Xu, Jiawen A1 Yang, Juanzhen A1 Zhu, Xialin A1 Lu, Yin A1 Duan, Wenhu A1 Huang, Xi A1 Wang, Jiaying A1 Zhou, Jinpei A1 Shen, Xu YR 2020 UL http://diabetes.diabetesjournals.org/content/69/9/1974.abstract AB 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 AMPKα activator efficiently ameliorated DPN in both streptozotocin (STZ)-induced type 1 and BKS db/db type 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 AMPKα, which has been verified by assay against the STZ-induced diabetic mice injected with adeno-associated virus 8–AMPKα–RNAi. To our knowledge, our work might be the first report on the amelioration of the direct AMPKα 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.