Immunoregulation effects of Exendin-4 on peripheral blood mononuclear cells in patients with type 1 diabetes mellitus

Abstract

Objective To investigate the immunoregulation effects of Exendin-4 on peripheral blood mononuclear cells (PBMC) in patients with type 1 diabetes mellitus (T1DM). Methods PBMC samples from 11 T1DM subjects were used to investigate the effects of Exendin-4 on PBMCs in vitro. Intervention group (0, 10, 100 nmol/L) and antagonist group (50 nmol/L Exendin 9(39)+100 nmol/L Exendin-4) were set according to the concentration of cyclic adenosine monophospphate (cAMP) in PBMCs. Cytokines [interleukin(IL)10, tumor necrosis factor α(TNF-α)] were measured by cytometric bead array and real-time quantitative PCR (RT-qPCR) analysis, respectively. Results (1) GLP-1R was detected in PBMC of T1DM. Compared with control group, the expression of GLP-1R mRNA was significantly increased in 100 nmol/L Exendin-4 treated group (1.97±0.24 vs 1, P 0.05). (3)10 nmol/L and 100 nmol/L Exendin-4 had significant effects on levels of cAMP (7.51±0.01 vs 2.56±0.01, 17.21±0.04 vs 2.56±0.01, respectively, both P<0.05) . (4) The mRNA expression levels of TNF-α, TNF-α levels in the cellular supernatant were significantly decreased after Exendin-4 intervention (F=5.54, 5.12, P<0.05), and was inhibited by GLP-1R antagonist Exendin-9 (39) (F=5.43, 5.97, P<0.05). The levels of IL-10 in supernatant were elevated (F=5.95, 6.01, P<0.05) although IL-10 mRNA levels maintained stable in PBMC. Conclusion Exendin-4 could down-regulate TNF-α secretion and up-regulate IL-10 secretion in PBMC of T1DM patients. These results suggest that exendin-4 might down-regulate pro-inflammatory responses. Key words: Exendin-4; Diabetes mellitus, type 1; Glucagon-like peptide-1 receptor; Immunoregulation