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Exendin-4 modulates diabetes onset in nonobese diabetic mice

Irene Hadjiyanni1, Laurie L Baggio, Philippe Poussier

  • 1Department of Medicine, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5.

Endocrinology
|December 8, 2007
PubMed

Insights

Glucagon-like peptide-1 receptor (GLP-1R) activation with exendin-4 delayed type 1 diabetes onset in mice. This treatment enhanced beta-cell mass and improved glucose tolerance without significant immune cell alteration.

Area of Science:

  • Immunology
  • Endocrinology
  • Diabetes Research

Background:

  • Glucagon-like peptide-1 receptor (GLP-1R) activation promotes beta-cell proliferation and survival.
  • Exenatide (exendin-4), a GLP-1R agonist, is under investigation for type 1 diabetes.
  • Limited data exist on GLP-1R activation's efficacy in preventing experimental type 1 diabetes.

Purpose of the Study:

  • To investigate the effects of exendin-4 (Ex-4) on the onset of type 1 diabetes in nonobese diabetic mice.
  • To assess the impact of Ex-4 on beta-cell mass, glucose tolerance, and immune cell populations.

Main Methods:

  • Nonobese diabetic mice were treated with Ex-4 at different doses and ages (4 or 9 weeks) prior to diabetes onset.
  • Diabetes onset, insulitis scores, beta-cell mass, glucose tolerance, and immune cell subsets (T cells, B cells) were evaluated after 26 weeks of treatment.
  • GLP-1R mRNA expression was analyzed in various immune organs.

Main Results:

  • Ex-4 treatment (2 microg twice daily) initiated at 4 weeks of age significantly delayed diabetes onset (P = 0.007).
  • Treated mice showed reduced insulitis, increased beta-cell mass, and improved glucose tolerance.
  • Ex-4 increased CD4+ and CD8+ T cells in lymph nodes and reduced regulatory T cells in the thymus, but did not significantly alter splenic immune cell populations.

Conclusions:

  • Sustained GLP-1R activation with exendin-4 can modestly delay type 1 diabetes onset in a murine model.
  • The observed delay occurs independently of major alterations in splenic immune cell numbers.
  • GLP-1R activation may influence immune cell distribution in lymphoid organs, potentially contributing to delayed diabetes onset.

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