Journal of Endocrinological Investigation

, Volume 31, Issue 4, pp 334–340 | Cite as

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

  • E. Hahm
  • Y. S. Lee
  • H. S. Jun
Original Articles


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.


Nitric oxide inducible nitric oxide synthase glucagon-like peptide-1 interferon-γ β cells 


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Copyright information

© Italian Society of Endocrinology (SIE) 2008

Authors and Affiliations

  1. 1.Rosalind Franklin Comprehensive Diabetes CenterChicago Medical SchoolNorth ChicagoUSA
  2. 2.Laboratory of Beta-cell Biology and Autoimmunity, Lee Gil Ya Cancer and Diabetes InstituteGachon University of Medicine and ScienceSongdo-dong, Yeonsu-ku, IncheonKorea

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