Lowered tumor necrosis factor receptors, but not increased insulin sensitivity, with infliximab

Paola Di Rocco, Melania Manco, Giuseppina Rosa, Aldo V. Greco, Geltrude Mingrone

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: To verify whether Infliximab could modify insulin sensitivity and TNF-α and GLUT4 mRNA expression in muscle and adipose tissue of morbidly obese subjects. Soluble TNF receptors I and II (TNFR-I and TNFR-II) were also assayed. Research Methods and Procedures: Six obese subjects were investigated before and 2 weeks after a single intravenous administration of 5 mg/kg Infliximab; insulin sensitivity was evaluated by euglycemic hyperinsulinemic clamp, and TNF-α and GLUT4 mRNA expression were assessed by reverse-transcriptase polymerase chain reaction on muscle and adipose tissue. TNF-α, TNFR-I, and TNFR-II were determined using the ELISA technique. Results: Infliximab infusion did not affect fasting plasma insulin or fasting plasma glucose levels; whole body glucose uptake did not change significantly. TNF-α and GLUT4 mRNA did not show any significant change in muscle or adipose tissue. Serum TNF-α was undetectable before and after treatment, whereas TNFR-I and TNFR-II concentrations significantly decreased (p <0.01). Discussion: An explanation for the absence of effect of Infliximab on insulin resistance in morbidly obese subjects may be the paracrine way of action of this cytokine. Because Infliximab is predominantly distributed within the vascular compartment, its effectiveness in penetrating muscle and adipose tissue is potentially low. The significant decrease of TNFR-I and TNFR-II might be ascribed to a targeted effect of Infliximab on the immune system.

Original languageEnglish
Pages (from-to)734-739
Number of pages6
JournalObesity Research
Volume12
Issue number4
Publication statusPublished - 2004

Keywords

  • Euglycemic hyperinsulinemic clamp
  • Infliximab
  • Insulin sensitivity
  • Tumor necrosis factor αreceptors

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Public Health, Environmental and Occupational Health
  • Endocrinology
  • Food Science
  • Endocrinology, Diabetes and Metabolism

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