Glucagon-like peptide-1 receptor signalling  selectively regulates murine lymphocyte proliferation  and maintenance of peripheral regulatory T cells.
OBJECTIVE
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
These studies establish that GLP-1R signalling may regulate lymphocyte proliferation and maintenance of peripheral regulatory T cells.
Department of Medicine, Samuel Lunenfeld Research Institute, Mt Sinai Hospital, 600 University Avenue TCP5-1004, Toronto, ON M5G 1X5, Canada.
I
I
Hadjiyanni
K A
KA
Siminovitch
J S
JS
Danska
D J
DJ
Drucker
D000818:Animals; D002455:Cell Division; D002465:Cell Movement; D000242:Cyclic AMP / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D005260:Female; D005434:Flow Cytometry; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD / Q000276:immunology*; D018345:Mice, Knockout; D009928:Organ Specificity; D018027:Receptors, Glucagon / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
C000593833:GLP1R protein, human; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D018027:Receptors, Glucagon; D000242:Cyclic AMP