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Suppressive effects of glucagon-like peptide-1 on interferon-γ-induced nitric oxide production in insulinproducing cells is mediated by inhibition of tumor necrosis factor-α production

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Abstract

During the development of Type 1 diabetes, inflammatory cytokines are known to induce the expression of inducible nitric oxide synthase (iNOS) in pancreatic islets, and subsequent production of nitric oxide (NO) contributes to β cell destruction. Glucagon-like peptide-1 (GLP-1) has been shown to reduce cytokine-in-duced apoptosis of β cells. In this study, we investigated whether GLP-1 affects cytokine-in-duced NO production, resulting in the inhibition of β-cell apoptosis. We treated MIN6N8a mouse β cells with interferon (IFN)-γ in the presence or absence of GLP-1 and found that IFN-γ treatment induced iNOS mRNA expression and NO production, which was significantly inhibited by treatment with GLP-1. Blocking of GLP-1 receptor signaling via the cyclic AMP and phosphatidylinositol 3-kinase pathway did not directly affect the suppressive effect of GLP-1 on IFN-γ-induced iNOS mRNA expression. Further studies revealed that IFN-γ induced the expression of TNF-α mRNA and protein, which synergistically induced NO production, and GLP-1 treatment inhibited this induction of TNF-α. To examine whether the reduction of TNF-α by GLP-1 treatment plays a role in suppressing NO production, we treated MIN6N8a cells with IFN-γ in the presence of anti-TNF-α neutralizing antibody and found that NO production was reduced. In addition, treatment of mouse islets with GLP-1 inhibited the expression of iNOS and TNF-α mRNA. These results suggest that GLP-1 inhibits IFN-γ-induced NO production by suppression of TNF-α production.

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Authors and Affiliations

  1. Rosalind Franklin Comprehensive Diabetes Center, Chicago Medical School, North Chicago, Illinois, USA

    E. Hahm, Y. S. Lee & H. S. Jun PhD

  2. Laboratory of Beta-cell Biology and Autoimmunity, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Songdo-dong, Yeonsu-ku, Incheon, Korea

    Y. S. Lee & H. S. Jun PhD

Authors
  1. E. Hahm
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  2. Y. S. Lee
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  3. H. S. Jun PhD
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Correspondence to H. S. Jun PhD.

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Hahm, E., Lee, Y.S. & Jun, H.S. Suppressive effects of glucagon-like peptide-1 on interferon-γ-induced nitric oxide production in insulinproducing cells is mediated by inhibition of tumor necrosis factor-α production. J Endocrinol Invest 31, 334–340 (2008). https://doi.org/10.1007/BF03346367

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  • DOI: https://doi.org/10.1007/BF03346367

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