title: The Hepatic Protection Effects of Hepassocin in Hyperglycemic Crisis.
abstract: High glucose generates reactive oxygen species (ROS) and contributes to glucotoxicity in hepatocytes, and hyperglycemia causes structural and functional damage to the liver. However, only a mild hepatic dysfunction was observed in subjects with hyperglycemic crisis, implying a factor exists to exert a hepatic protective effect. Hepassocin is a hepatokine that modulates the proliferation and metabolism of hepatocytes and also exerts protective activity in liver injury. However, its role in hyperglycemic crisis-induced hepatic dysfunction remains unknown.
  
  
  
  To investigate the possible hepatic protection effects of hepassocin in hyperglycemic crisis.
  
  
  
  Plasma hepassocin concentrations and routine biochemistry were measured in 21 patients with hyperglycemic crisis before and after standard treatments. The effects of hepassocin on hepatic functions were evaluated in streptozotocin-induced hyperglycemic mice (STZ mice). HepG2 cells were used to clarify the possible mechanisms regulating hepassocin expression.
  
  
  
  Plasma hepassocin concentrations decreased significantly in subjects with hyperglycemic crisis after standard treatment accompanied by improved hepatic functions. Correction of hyperglycemia in STZ mice also decreased the hepatic hepassocin expression. Injection of recombinant hepassocin improved hepatic functions and histologic changes and increased the expression of antioxidative stress proteins, including superoxide dismutase 1 (SOD1). In HepG2 cells, high glucose increased hepassocin expression through signal transducer and activator of transcription 3 and hepatocyte nuclear factor-related pathways. We also demonstrated that hepassocin increased SOD1 expression through an extracellular signal-regulated kinase 1/2 nuclear factor erythroid-2-related factor 2 pathway, decreasing ethyl acetate-induced ROS production and improving cell viability.
  
  
  
  Increased hepassocin secretion in hyperglycemic crisis might offset the deleterious effects of hyperglycemia on hepatocytes.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.
authors.forename: Horng-Yih
authors.initials: HY
authors.lastname: Ou
authors.affiliation: Department of Family Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.|Research Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.
authors.forename: Hung-Tsung
authors.initials: HT
authors.lastname: Wu
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.
authors.forename: Ching-Han
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.
authors.forename: Ye-Fong
authors.initials: YF
authors.lastname: Du
authors.affiliation: Department of Urology, National Cheng Kung University Hospital, Tainan 70403, Taiwan.
authors.forename: Che-Yuan
authors.initials: CY
authors.lastname: Hu
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.
authors.forename: Hao-Chang
authors.initials: HC
authors.lastname: Hung
authors.affiliation: Institute for Science and Technology in Medicine, Keele University, Keele ST5 5BG, United Kingdom.
authors.forename: Pansee
authors.initials: P
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei 10048, Taiwan.
authors.forename: Hung-Yuan
authors.initials: HY
authors.lastname: Li
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
authors.forename: Shu-Huei
authors.initials: SH
authors.lastname: Wang
authors.affiliation: Department of Family Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.
authors.forename: Chih-Jen
authors.initials: CJ
authors.lastname: Chang
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005340:Fibrinogen; D056945:Hep G2 Cells / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000175:diagnosis* / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D017093:Liver Failure / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012494:Sampling Studies; D013311:Streptozocin / Q000494:pharmacology*; D014162:Transfection
chemical_list: C485894:FGL1 protein, human; D007004:Hypoglycemic Agents; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D013311:Streptozocin; D005340:Fibrinogen