title: Insulin regulates glucose consumption and lactate production through reactive oxygen species and pyruvate kinase M2.
abstract: Although insulin is known to regulate glucose metabolism and closely associate with liver cancer, the molecular mechanisms still remain to be elucidated. In this study, we attempt to understand the mechanism of insulin in promotion of liver cancer metabolism. We found that insulin increased pyruvate kinase M2 (PKM2) expression through reactive oxygen species (ROS) for regulating glucose consumption and lactate production, key process of glycolysis in hepatocellular carcinoma HepG2 and Bel7402 cells. Interestingly, insulin-induced ROS was found responsible for the suppression of miR-145 and miR-128, and forced expression of either miR-145 or miR-128 was sufficient to abolish insulin-induced PKM2 expression. Furthermore, the knockdown of PKM2 expression also inhibited cancer cell growth and insulin-induced glucose consumption and lactate production, suggesting that PKM2 is a functional downstream effecter of insulin. Taken together, this study would provide a new insight into the mechanism of insulin-induced glycolysis.
authors.affiliation: Department of Pathology, State Key Lab of Reproductive Medicine, Cancer Center, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Pathology, State Key Lab of Reproductive Medicine, Cancer Center, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pathology, State Key Lab of Reproductive Medicine, Cancer Center, Nanjing Medical University, Nanjing 210029, China ; Department of Pathology, Anhui Medical University, Hefei 230032, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Pathology, State Key Lab of Reproductive Medicine, Cancer Center, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Ji-Tai
authors.initials: JT
authors.lastname: Zheng
authors.affiliation: Department of Pathology, State Key Lab of Reproductive Medicine, Cancer Center, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Cheng-Fei
authors.initials: CF
authors.lastname: Jiang
authors.affiliation: Department of Pathology, State Key Lab of Reproductive Medicine, Cancer Center, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Pathology, State Key Lab of Reproductive Medicine, Cancer Center, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Chong-Yong
authors.initials: CY
authors.lastname: Li
authors.affiliation: Department of Pathology, State Key Lab of Reproductive Medicine, Cancer Center, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Ling-Zhi
authors.initials: LZ
authors.lastname: Liu
authors.affiliation: Department of Pathology, State Key Lab of Reproductive Medicine, Cancer Center, Nanjing Medical University, Nanjing 210029, China ; Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Bing-Hua
authors.initials: BH
authors.lastname: Jiang
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D019344:Lactic Acid / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism; D011770:Pyruvate Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D007328:Insulin; C545189:MIRN128 microRNA, human; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D019344:Lactic Acid; D011770:Pyruvate Kinase; D005947:Glucose