Glucagon-like peptide-1 receptor signalling selectively regulates murine lymphocyte proliferation and maintenance of peripheral regulatory T cells

Diabetologia. 2010 Apr;53(4):730-40. doi: 10.1007/s00125-009-1643-x. Epub 2010 Jan 8.


Aims/hypothesis: Glucagon-like peptide-1 receptor (GLP-1R) agonists improve glucose control in animals and humans with type 1 diabetes. However, there is little information on the role of the GLP-1R in the immune system. We studied the role of the GLP-1R in immune function in wild-type (WT) and nonobese diabetic (NOD) and Glp1r-/- mice.

Methods: Glp1r mRNA expression was examined in sorted immune subpopulations by RT-PCR. The effects of GLP-1R activation were assessed on cAMP production and proliferation, migration and survival of primary immune cells from WT and NOD mice. The ability of primary cells from Glp1r-/- mice to proliferate, migrate or survive apoptosis was determined. Immunophenotyping studies were performed to assess the frequency of immune subpopulations in Glp1r-/- mice.

Results: Ex vivo activation of the GLP-1R resulted in a modest but significant elevation of cAMP in primary thymocytes and splenocytes from both WT and NOD mice. GLP-1R activation did not increase proliferation of primary thymocytes, splenocytes or peripheral lymph node cells. In contrast, Glp1r-/- thymocytes exhibited a hypoproliferative response, whilst peripheral Glp1r-/- lymphocytes were hyperproliferative in response to mitogenic stimulation. Activation or loss of GLP-1R signalling did not modify apoptosis or chemotaxis in primary lymphocytes. Male Glp1r-/- mice exhibited a significantly lower percentage of peripheral regulatory T cells, although no differences were observed in the numbers of CD4+ and CD8+ T cells and B cells in the spleen and lymph nodes of Glp1r-/- mice.

Conclusions/interpretation: These studies establish that GLP-1R signalling may regulate lymphocyte proliferation and maintenance of peripheral regulatory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division
  • Cell Movement
  • Cyclic AMP / metabolism
  • Diabetes Mellitus, Type 1 / physiopathology
  • Female
  • Flow Cytometry
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Lymphocyte Activation / immunology*
  • Male
  • Mice
  • Mice, Inbred NOD / immunology*
  • Mice, Knockout
  • Organ Specificity
  • Receptors, Glucagon / deficiency
  • Receptors, Glucagon / genetics
  • Receptors, Glucagon / immunology*
  • Signal Transduction
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology*


  • GLP1R protein, human
  • Glp1r protein, mouse
  • Glucagon-Like Peptide-1 Receptor
  • Receptors, Glucagon
  • Cyclic AMP