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Diabetologia

Erschienen in:

01.04.2010 | Article

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

verfasst von: I. Hadjiyanni, K. A. Siminovitch, J. S. Danska, D. J. Drucker

Erschienen in: Diabetologia | Ausgabe 4/2010

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Abstract

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 non-obese 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.

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Titel: Glucagon-like peptide-1 receptor signalling selectively regulates murine lymphocyte proliferation and maintenance of peripheral regulatory T cells
verfasst von: I. Hadjiyanni
K. A. Siminovitch
J. S. Danska
D. J. Drucker
Publikationsdatum: 01.04.2010
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 4/2010
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-009-1643-x

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