title: Interleukin-18 Reduces Blood Glucose and Modulates Plasma Corticosterone in a Septic Mouse Model.
abstract: Dysregulation of glucose metabolism, including hyperglycemia with insulin resistance, is commonly observed in critically ill patients. Interleukin-18 (IL-18) improves the insulin resistance associated with obesity, but the relationship between IL-18 and glucose metabolism in sepsis was unclear. The purpose of this study was to investigate the influence of IL-18 on hyperglycemia during sepsis.
  
  
  
  Sepsis was induced using cecal ligation and puncture (CLP) in wild-type (WT) mice, IL-18 knockout (KO) mice, and IL-18 KO mice pretreated with recombinant IL-18. Blood glucose and plasma insulin, glucagon, and corticosterone were measured. The mRNAs for gluconeogenic enzymes (g6pc, pck1) and activation of insulin signaling were also analyzed.
  
  
  
  In both WT and IL-18 KO mice, CLP operation led to hyperglycemia that lasted longer (18 h) than after sham operation (6 h). Blood glucose levels in IL-18 KO mice were significantly higher than in WT mice, without alteration of insulin or glucagon levels. In IL-18 KO mice, insulin signaling in the liver and skeletal muscle was decreased during hyperglycemia as compared with WT mice without suppression of hepatic glucose production enzymes. Pretreatment with recombinant IL-18 reduced blood glucose levels after CLP. Additionally, corticosterone levels were higher after CLP in the presence of either endogenous or exogenous IL-18.
  
  
  
  IL-18 may reduce blood glucose by modulating insulin signaling in the liver during sepsis-induced hyperglycemia. IL-18 is an important factor associated with alterations in blood glucose during sepsis.
authors.affiliation: *Department of Biophysics, Kobe University Graduate School of Health Sciences, Hyogo, Japan †Department of Emergency, Disaster and Critical Care Medicine, Hyogo College of Medicine, Hyogo, Japan ‡Division of Orthopedic Surgery, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Hayato
authors.initials: H
authors.lastname: Yamashita
authors.forename: Michiko
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Taketo
authors.initials: T
authors.lastname: Inoue
authors.forename: Makoto
authors.initials: M
authors.lastname: Usami
authors.forename: Yu
authors.initials: Y
authors.lastname: Usami
authors.forename: Joji
authors.initials: J
authors.lastname: Kotani
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood*; D004195:Disease Models, Animal; D005952:Glucose-6-Phosphatase / Q000235:genetics; D007328:Insulin / Q000097:blood; D020382:Interleukin-18 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics; D018805:Sepsis / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020382:Interleukin-18; D005952:Glucose-6-Phosphatase; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D003345:Corticosterone