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

Abstract

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.

• Authors: Lan He, Chun Kwok Wong, Kitty Kt Cheung, Ho Chung Yau, Anthony Fu, Hai-Lu Zhao, Karen Ml Leung, Alice Ps Kong, Gary Wk Wong, Paul Ks Chan, Gang Xu, Juliana Cn Chan
• Journal: Journal of diabetes investigation (J Diabetes Investig) Vol. 4 Issue 4 Pg. 382-92 (Jul 08 2013) ISSN: 2040-1116 [Print] Japan
• PMID: 24843684 (Publication Type: Journal Article)