title: Inflammatory induction of human resistin causes insulin resistance in endotoxemic mice.
abstract: OBJECTIVE
  Although adipocyte-derived murine resistin links insulin resistance to obesity, the role of human resistin, predominantly expressed in mononuclear cells and induced by inflammatory signals, remains unclear. Given the mounting evidence that obesity and type 2 diabetes are inflammatory diseases, we sought to determine the relationship between inflammatory increases in human resistin and insulin resistance.
  
  
  METHODS
  To investigate the role of human resistin on glucose homeostasis in inflammatory states, we generated mice lacking murine resistin but transgenic for a bacterial artificial chromosome containing human resistin (BAC-Retn), whose expression was similar to that in humans. The metabolic and molecular phenotypes of BAC-Retn mice were assessed after acute and chronic endotoxemia (i.e., exposure to inflammatory lipopolysaccharide).
  
  
  RESULTS
  We found that BAC-Retn mice have circulating resistin levels within the normal human range, and similar to humans, lipopolysaccharide markedly increased serum resistin levels. Acute endotoxemia caused hypoglycemia in mice lacking murine resistin, and this was attenuated in BAC-Retn mice. In addition, BAC-Retn mice developed severe hepatic insulin resistance under chronic endotoxemia, accompanied by increased inflammatory responses in liver and skeletal muscle.
  
  
  CONCLUSIONS
  These results strongly support the role of human resistin in the development of insulin resistance in inflammation. Thus, human resistin may link insulin resistance to inflammatory diseases such as obesity, type 2 diabetes, and atherosclerosis.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Hyeong-Kyu
authors.initials: HK
authors.lastname: Park
authors.forename: Mohammed
authors.initials: M
authors.lastname: Qatanani
authors.forename: Erika R
authors.initials: ER
authors.lastname: Briggs
authors.forename: Rexford S
authors.initials: RS
authors.lastname: Ahima
authors.forename: Mitchell A
authors.initials: MA
authors.lastname: Lazar
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019446:Endotoxemia / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D007249:Inflammation / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D052243:Resistin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D008070:Lipopolysaccharides; D052243:Resistin