Insulin Attenuates Apoptosis and Exerts Anti-Inflammatory Effects in Endotoxemic Human Macrophages

Mareike Leffler, Thomas Hrach, Michael Stuerzl, Raymund E. Horch, David N. Herndon, Marc G. Jeschke

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Background: Insulin decreases the incidence of sepsis and improves mortality of critically ill patients. In endotoxemic as well as in thermally injured rats, insulin attenuates the systemic inflammatory response by decreasing the proinflammatory and increasing the antiinflammatory cascade. The aim of the present study was to determine the effects of insulin on cell survival, cell activity, apoptosis, and proinflammatory response in a human macrophage-like cell line (THP-1 cells) stressed with lipopolysaccharide (LPS). Materials and methods: Human macrophages were stressed with LPS and received either saline or insulin. Cell viability was analyzed by MTS, apoptosis was detected using JC-1 and terminal deoxynucleotidyl transferase-mediated nick end labeling-staining, and to elucidate on the signaling pathway, we used wortmannin as a phosphatidylinositol-3-kinase inhibitor. Tumor necrosis factor (TNF) and interleukin-1beta (IL-1β) were measured to determine the effect of insulin on proinflammatory cytokine expression. Results: Insulin caused a significant increase in cell viability and significantly reduced apoptosis in LPS-stimulated human macrophages in a dose-dependent manner. The antiapoptotic effect of insulin could be completely blocked with the addition of wortmannin. Insulin significantly decreased TNF and IL-1β in endotoxemic human macrophages. Conclusions: Our results indicate that insulin exerts antiapoptotic effects and reduces the expression of proinflammatory cytokines in endotoxemic human macrophages. The antiapoptotic effects are mediated via the phospatidylinositol-3-kinase-pathway.

Original languageEnglish (US)
Pages (from-to)398-406
Number of pages9
JournalJournal of Surgical Research
Volume143
Issue number2
DOIs
StatePublished - Dec 1 2007

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Keywords

  • apoptosis
  • endotoxemia
  • inflammation
  • insulin
  • macrophage
  • phopsphatidylinositol-3-kinase
  • sepsis
  • wortmannin

ASJC Scopus subject areas

  • Surgery

Cite this

Leffler, M., Hrach, T., Stuerzl, M., Horch, R. E., Herndon, D. N., & Jeschke, M. G. (2007). Insulin Attenuates Apoptosis and Exerts Anti-Inflammatory Effects in Endotoxemic Human Macrophages. Journal of Surgical Research, 143(2), 398-406. https://doi.org/10.1016/j.jss.2007.01.030