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


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.
Department of Medicine and Therapeutics The Chinese University of Hong Kong Shatin Hong Kong SAR China.
Lan
L
He
Department of Chemical Pathology The Chinese University of Hong Kong Shatin Hong Kong SAR China.
Chun Kwok
CK
Wong
Department of Medicine and Therapeutics The Chinese University of Hong Kong Shatin Hong Kong SAR China.
Kitty Kt
KK
Cheung
Department of Pediatrics Prince of Wales Hospital The Chinese University of Hong Kong Shatin Hong Kong SAR China.
Ho Chung
HC
Yau
Department of Pediatrics Prince of Wales Hospital The Chinese University of Hong Kong Shatin Hong Kong SAR China.
Anthony
A
Fu
Department of Medicine and Therapeutics The Chinese University of Hong Kong Shatin Hong Kong SAR China.
Hai-Lu
HL
Zhao
Department of Chemical Pathology The Chinese University of Hong Kong Shatin Hong Kong SAR China.
Karen Ml
KM
Leung
Department of Medicine and Therapeutics The Chinese University of Hong Kong Shatin Hong Kong SAR China ; Hong Kong Institute of Diabetes and Obesity The Chinese University of Hong Kong Shatin Hong Kong SAR China ; Li Ka Shing Institute of Health Sciences The Chinese University of Hong Kong Shatin Hong Kong SAR China.
Alice Ps
AP
Kong
Department of Pediatrics Prince of Wales Hospital The Chinese University of Hong Kong Shatin Hong Kong SAR China.
Gary Wk
GW
Wong
Department of Microbiology The Chinese University of Hong Kong Shatin Hong Kong SAR China.
Paul Ks
PK
Chan
Department of Medicine and Therapeutics The Chinese University of Hong Kong Shatin Hong Kong SAR China ; Hong Kong Institute of Diabetes and Obesity The Chinese University of Hong Kong Shatin Hong Kong SAR China ; Li Ka Shing Institute of Health Sciences The Chinese University of Hong Kong Shatin Hong Kong SAR China.
Gang
G
Xu
Department of Medicine and Therapeutics The Chinese University of Hong Kong Shatin Hong Kong SAR China ; Hong Kong Institute of Diabetes and Obesity The Chinese University of Hong Kong Shatin Hong Kong SAR China ; Li Ka Shing Institute of Health Sciences The Chinese University of Hong Kong Shatin Hong Kong SAR China.
Juliana Cn
JC
Chan
Diabetes; Exendin‐4; Inflammation