Anti-inflammatory Effects of Exendin-4, a Glucagon-like Peptide-1 Analog, on Human Peripheral Lymphocytes in Patients with Type 2 Diabetes

Overview

Journal J Diabetes Investig

Specialty Endocrinology

Date 2014 May 21

PMID 24843684

Citations 34

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

Affiliations

Soon will be listed here.

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.

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