title: An inflammatory cascade leading to hyperresistinemia in humans.
abstract: BACKGROUND
  Obesity, the most common cause of insulin resistance, is increasingly recognized as a low-grade inflammatory state. Adipocyte-derived resistin is a circulating protein implicated in insulin resistance in rodents, but the role of human resistin is uncertain because it is produced largely by macrophages.
  
  
  RESULTS
  The effect of endotoxin and cytokines on resistin gene and protein expression was studied in human primary blood monocytes differentiated into macrophages and in healthy human participants. Inflammatory endotoxin induced resistin in primary human macrophages via a cascade involving the secretion of inflammatory cytokines that circulate at increased levels in individuals with obesity. Induction of resistin was attenuated by drugs with dual insulin-sensitizing and anti-inflammatory properties that converge on NF-kappaB. In human study participants, experimental endotoxemia, which produces an insulin-resistant state, causes a dramatic rise in circulating resistin levels. Moreover, in patients with type 2 diabetes, serum resistin levels are correlated with levels of soluble tumor necrosis factor alpha receptor, an inflammatory marker linked to obesity, insulin resistance, and atherosclerosis.
  
  
  CONCLUSIONS
  Inflammation is a hyperresistinemic state in humans, and cytokine induction of resistin may contribute to insulin resistance in endotoxemia, obesity, and other inflammatory states.
authors.affiliation: Division of Endocrinology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Lehrke
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
authors.forename: Segan C
authors.initials: SC
authors.lastname: Millington
authors.forename: Nayyar
authors.initials: N
authors.lastname: Iqbal
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
authors.forename: Mitchell A
authors.initials: MA
authors.lastname: Lazar
mesh_terms: D002454:Cell Differentiation; D016207:Cytokines / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D004731:Endotoxins; D007249:Inflammation; D007333:Insulin Resistance / Q000276:immunology*; D008264:Macrophages; D009765:Obesity / Q000503:physiopathology*
chemical_list: D016207:Cytokines; D004731:Endotoxins