title: Metformin prevents LYRM1-induced insulin resistance in 3T3-L1 adipocytes via a mitochondrial-dependent mechanism.
abstract: We previously proposed that LYR motif containing 1 (LYRM1)-induced mitochondrial reactive oxygen species (ROS) production contributes to obesity-related insulin resistance. Metformin inhibits ROS production and promotes mitochondrial biogenesis in specific tissues. We assessed the effects of metformin on insulin resistance in LYRM1-over-expressing 3T3-L1 adipocytes. Metformin enhanced basal and insulin-stimulated glucose uptake and GLUT4 translocation, reduced IRS-1 and Akt phosphorylation and ROS levels, and affected the expression of regulators of mitochondrial biogenesis in LYRM1-over-expressing adipocytes. Metformin may ameliorate LYRM1-induced insulin resistance and mitochondrial dysfunction in part via a direct antioxidant effect and in part by activating the adenosine monophosphate-activated protein kinase (AMPK)-PGC1/NRFs pathway.
authors.affiliation: The First Affiliated Hospital with Nanjing Medical University, Nanjing 210036, China.
authors.forename: Zhen-Ying
authors.initials: ZY
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Maternal and Child Health Hospital of Nanjing Medical University, Nanjing 210004, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Maternal and Child Health Hospital of Nanjing Medical University, Nanjing 210004, China.
authors.forename: Yong-mei
authors.initials: YM
authors.lastname: Dai
authors.affiliation: Department of Child Health, Huai'an Maternity and Child Health Hospital, Huai'an 223002, China.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Wang
authors.affiliation: Institute of Pediatrics, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Guan-zhong
authors.initials: GZ
authors.lastname: Zhu
authors.affiliation: The 82nd Hospital of the People's Liberation Army, Huai'an 223001, China.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Maternal and Child Health Hospital of Nanjing Medical University, Nanjing 210004, China.
authors.forename: Chen-Bo
authors.initials: CB
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Maternal and Child Health Hospital of Nanjing Medical University, Nanjing 210004, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Maternal and Child Health Hospital of Nanjing Medical University, Nanjing 210004, China xgcao@njmu.edu.cn xrguo@njmu.edu.cn.
authors.forename: Xin-Guo
authors.initials: XG
authors.lastname: Cao
authors.affiliation: Institute of Pediatrics, Nanjing Medical University, Nanjing 210029, China xgcao@njmu.edu.cn xrguo@njmu.edu.cn.
authors.forename: Xi-Rong
authors.initials: XR
authors.lastname: Guo
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002460:Cell Line; D007004:Hypoglycemic Agents / Q000378:metabolism*; D007333:Insulin Resistance; D008687:Metformin / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000032:analysis
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D007004:Hypoglycemic Agents; C570850:LYR motif containing 1 protein, mouse; D017382:Reactive Oxygen Species; D008687:Metformin
keywords: LYRM1; insulin resistance; metformin; mitochondrial biogenesis