Influence of TNF-α and IL-6 infusions on insulin sensitivity and expression of IL-18 in humans

Rikke Krogh-Madsen, Peter Plomgaard, Kirsten Møller, Bettina Mittendorfer, Bente K. Pedersen

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

Abstract

Inflammation is associated with insulin resistance, and both tumor necrosis factor (TNF)-α and interleukin (IL)-6 may affect glucose uptake. TNF induces insulin resistance, whereas the role of IL-6 is controversial. High plasma levels of IL-18 are associated with insulin resistance in epidemiological studies. We investigated the effects of TNF and IL-6 on IL-18 gene expression in skeletal muscle and adipose tissue. Nine human volunteers underwent three consecutive interventions, receiving an infusion of recombinant human (rh)IL-6, rhTNF, and saline. Insulin sensitivity was assessed by measurement of whole body glucose uptake with the stable isotope tracer method during a euglycemic hyperinsulinemic clamp (20 mU·min-1·kg-1), which was initiated 1 h after the IL-6-TNF-saline infusion. Cytokine responses were measured in plasma, muscle, and fat biopsies. Plasma concentrations of TNF and IL-6 increased 10- and 38-fold, respectively, during the cytokine infusions. Whole body insulin-mediated glucose uptake was significantly reduced during TNF infusion but remained unchanged during IL-6 infusion. TNF induced IL-18 gene expression in muscle tissue, but not in adipose tissue, whereas IL-6 infusion had no effect on IL-18 gene expression in either tissue. We conclude that TNF-induced insulin resistance of whole body glucose uptake is associated with increased IL-18 gene expression in muscle tissue, indicating that TNF and IL-18 interact, and both may have important regulatory roles in the pathogenesis of insulin resistance.

Original languageEnglish
Pages (from-to)E108-E114
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume291
Issue number1
DOIs
StatePublished - 2006

Keywords

  • Cytokines
  • Diabetes
  • Inflammation
  • Interleukin-18
  • Interleukin-6
  • Tumor necrosis factor-α

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