Anti-inflammatory effects of exendin-4, a glucagon-like peptide-1 analog, on human peripheral lymphocytes in patients with type 2 diabetes

Aims/Introduction Type 2 diabetes is characterized by dysregulation of immunity, oxidative stress and reduced incretin effects. Experimental studies suggest that glucagon‐like peptide (GLP‐1) might have immunomodulating effects. We hypothesize that GLP‐1 receptor agonist, exendin‐4, might reduce inflammatory response in type 2 diabetes. Materials and Methods Using peripheral blood mononuclear cells (PBMC) sampled from 10 type 2 diabetes and 10 sex‐ and age‐matched control subjects and supernatants from PBMC culture, the expression of phospho‐mitogen activated protein kinase (MAPK) signaling pathways in CD4+ T helper lymphocytes and monocytes was analyzed using flow cytometry. Cytokines/chemokines and superoxide anion before and after treatment with exendin‐4 were measured by cytometric bead array and chemiluminesence assay, respectively. Results Compared with control subjects, PBMC from type 2 diabetes patients showed activated MAPK (P38, c‐Jun NH2‐terminal protein kinase and extracellular signal‐regulated kinase) signaling pathway, elevated superoxide anion, increased pro‐inflammatory cytokines (tumor necrosis factor‐α, interleukin‐1β, interleukin‐6) and chemokines (CCL5/regulated on activation normal T‐cell expressed and secreted and CXCL10/interferon‐γ‐induced protein 10). These changes were attenuated by exendin‐4, possibly through the suppression of p38 MAPK. Conclusions These results suggest that exendin‐4 might downregulate pro‐inflammatory responses and reduce oxidative stress by suppressing MAPK signaling pathways in type 2 diabetes.