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Research ArticleENDOCRINE AND REPRODUCTIVE

Nicotine Reduces the Incidence of Type I Diabetes in Mice

J. G. Mabley, P. Pacher, G. J. Southan, A. L. Salzman and C. Szabó
Journal of Pharmacology and Experimental Therapeutics March 2002, 300 (3) 876-881; DOI: https://doi.org/10.1124/jpet.300.3.876
J. G. Mabley
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P. Pacher
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G. J. Southan
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A. L. Salzman
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C. Szabó
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Abstract

Nicotine has been previously shown to have immunosuppressive actions. Type I diabetes is an autoimmune disease resulting from the specific destruction of the insulin-producing pancreatic β-cells. Thus, we hypothesized that nicotine may exert protective effects against type I diabetes. The multiple low-dose streptozotocin (MLDS)-induced model and spontaneous nonobese diabetic (NOD) mouse model of type I diabetes were used to assess whether nicotine could prevent this autoimmune disease. Blood glucose levels, diabetes incidence, pancreas insulin content, and cytokine levels were measured in both models of diabetes, both to asses the level of protection exerted by nicotine and to further investigate its mechanism of action. Nicotine treatment reduced the hyperglycemia and incidence of disease in both the MLDS and NOD mouse models of diabetes. Nicotine also protected against the diabetes-induced decrease in pancreatic insulin content observed in both animal models. The pancreatic levels of the Th1 cytokines interleukin (IL)-12, IL-1, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were increased in both MLDS-induced and spontaneous NOD diabetes, an effect prevented by nicotine treatment. Nicotine treatment increased the pancreatic levels of the Th2 cytokines IL-4 and IL-10. Nicotine treatment reduces the incidence of type I diabetes in two animal models by changing the profile of pancreatic cytokine expression from Th1 to Th2.

Footnotes

  • This study was supported by an innovative grant from the Juvenile Diabetes Foundation International to J.G.M. (JDRF file no. 5-2000-430). P.P. is on leave from the Department of Pharmacology, Semmelweis University Medical School (Budapest, Hungary).

  • Abbreviations:
    iNOS
    inducible nitric oxide synthase
    IL
    interleukin
    TNF-α
    tumor necrosis factor-α
    IFN-γ
    interferon-γ
    MLDS
    multiple low-dose streptozotocin
    NOD
    nonobese diabetic
    ELISA
    enzyme-linked immunosorbent assay
    • Received October 16, 2001.
    • Accepted November 16, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 300 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 300, Issue 3
1 Mar 2002
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Research ArticleENDOCRINE AND REPRODUCTIVE

Nicotine Reduces the Incidence of Type I Diabetes in Mice

J. G. Mabley, P. Pacher, G. J. Southan, A. L. Salzman and C. Szabó
Journal of Pharmacology and Experimental Therapeutics March 1, 2002, 300 (3) 876-881; DOI: https://doi.org/10.1124/jpet.300.3.876

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Research ArticleENDOCRINE AND REPRODUCTIVE

Nicotine Reduces the Incidence of Type I Diabetes in Mice

J. G. Mabley, P. Pacher, G. J. Southan, A. L. Salzman and C. Szabó
Journal of Pharmacology and Experimental Therapeutics March 1, 2002, 300 (3) 876-881; DOI: https://doi.org/10.1124/jpet.300.3.876
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