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

He L, Wong CK, Cheung KK, Yau HC, Fu A, Zhao HL, Leung KM, Kong AP, Wong GW, Chan PK, Xu G, Chan JC - J Diabetes Investig (2013)

Bottom Line: Experimental studies suggest that glucagon-like peptide (GLP-1) might have immunomodulating effects.These changes were attenuated by exendin-4, possibly through the suppression of p38 MAPK.These results suggest that exendin-4 might downregulate pro-inflammatory responses and reduce oxidative stress by suppressing MAPK signaling pathways in type 2 diabetes.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and Therapeutics The Chinese University of Hong Kong Shatin Hong Kong SAR China.

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.

No MeSH data available.


Related in: MedlinePlus

Basal and ex vivo expression of phospho‐mitogen‐activated protein kinases (MAPK) in exendin‐4 treated CD4+ T lymphocytes and monocytes from peripheral blood mononuclear cells in patients with type 2 diabetes (T2DM) and healthy subjects. (4‐1) Representative histograms show the intracellular expression of (a,b) phospho‐extracellular signal‐regulated kinase (ERK), (c,d) phosphor‐p38 and (e,f) phosphor‐c‐Jun NH2‐terminal protein kinase (JNK) in peripheral blood mononuclear cells incubated without or with exendin‐4 (50 nmol/L) for 10 min. (4‐2) Results are expressed in bar charts. (a) Phosphorylation of ERK, (b), phosphorylation of p38 MAPK and (c) phosphorylation of JNK in monocytes and CD4+ T lymphocytes from patients with type2 diabetes and control subjects were analyzed by flow cytometry. Results are presented with box‐and‐whisker plots.
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jdi12063-fig-0004: Basal and ex vivo expression of phospho‐mitogen‐activated protein kinases (MAPK) in exendin‐4 treated CD4+ T lymphocytes and monocytes from peripheral blood mononuclear cells in patients with type 2 diabetes (T2DM) and healthy subjects. (4‐1) Representative histograms show the intracellular expression of (a,b) phospho‐extracellular signal‐regulated kinase (ERK), (c,d) phosphor‐p38 and (e,f) phosphor‐c‐Jun NH2‐terminal protein kinase (JNK) in peripheral blood mononuclear cells incubated without or with exendin‐4 (50 nmol/L) for 10 min. (4‐2) Results are expressed in bar charts. (a) Phosphorylation of ERK, (b), phosphorylation of p38 MAPK and (c) phosphorylation of JNK in monocytes and CD4+ T lymphocytes from patients with type2 diabetes and control subjects were analyzed by flow cytometry. Results are presented with box‐and‐whisker plots.

Mentions: To characterize the intracellular mechanism for the release of cytokines and chemokines from PBMC, we investigated the phosphorylation of intracellular ERK and p38 MAPK in CD4+ T lymphocytes and monocytes. As shown in Figure 3, the representative histograms of flow cytometric analysis illustrated increased levels of phospho‐ERK, phospho‐p38, and phospho‐JNK in CD4+ T lymphocytes and monocytes in type 2 diabetes patients compared with control subjects. Figure 4 showed higher phosphorylation of ERK and p38 at baseline in type 2 diabetes patients than control subjects (all P < 0.05). Exendin‐4 suppressed phosphorylation of ERK and p38 MAPK (all P < 0.05) in CD4+ T lymphocytes and monocytes from type 2 diabetes patients (P > 0.05).


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

He L, Wong CK, Cheung KK, Yau HC, Fu A, Zhao HL, Leung KM, Kong AP, Wong GW, Chan PK, Xu G, Chan JC - J Diabetes Investig (2013)

Basal and ex vivo expression of phospho‐mitogen‐activated protein kinases (MAPK) in exendin‐4 treated CD4+ T lymphocytes and monocytes from peripheral blood mononuclear cells in patients with type 2 diabetes (T2DM) and healthy subjects. (4‐1) Representative histograms show the intracellular expression of (a,b) phospho‐extracellular signal‐regulated kinase (ERK), (c,d) phosphor‐p38 and (e,f) phosphor‐c‐Jun NH2‐terminal protein kinase (JNK) in peripheral blood mononuclear cells incubated without or with exendin‐4 (50 nmol/L) for 10 min. (4‐2) Results are expressed in bar charts. (a) Phosphorylation of ERK, (b), phosphorylation of p38 MAPK and (c) phosphorylation of JNK in monocytes and CD4+ T lymphocytes from patients with type2 diabetes and control subjects were analyzed by flow cytometry. Results are presented with box‐and‐whisker plots.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4020234&req=5

jdi12063-fig-0004: Basal and ex vivo expression of phospho‐mitogen‐activated protein kinases (MAPK) in exendin‐4 treated CD4+ T lymphocytes and monocytes from peripheral blood mononuclear cells in patients with type 2 diabetes (T2DM) and healthy subjects. (4‐1) Representative histograms show the intracellular expression of (a,b) phospho‐extracellular signal‐regulated kinase (ERK), (c,d) phosphor‐p38 and (e,f) phosphor‐c‐Jun NH2‐terminal protein kinase (JNK) in peripheral blood mononuclear cells incubated without or with exendin‐4 (50 nmol/L) for 10 min. (4‐2) Results are expressed in bar charts. (a) Phosphorylation of ERK, (b), phosphorylation of p38 MAPK and (c) phosphorylation of JNK in monocytes and CD4+ T lymphocytes from patients with type2 diabetes and control subjects were analyzed by flow cytometry. Results are presented with box‐and‐whisker plots.
Mentions: To characterize the intracellular mechanism for the release of cytokines and chemokines from PBMC, we investigated the phosphorylation of intracellular ERK and p38 MAPK in CD4+ T lymphocytes and monocytes. As shown in Figure 3, the representative histograms of flow cytometric analysis illustrated increased levels of phospho‐ERK, phospho‐p38, and phospho‐JNK in CD4+ T lymphocytes and monocytes in type 2 diabetes patients compared with control subjects. Figure 4 showed higher phosphorylation of ERK and p38 at baseline in type 2 diabetes patients than control subjects (all P < 0.05). Exendin‐4 suppressed phosphorylation of ERK and p38 MAPK (all P < 0.05) in CD4+ T lymphocytes and monocytes from type 2 diabetes patients (P > 0.05).

Bottom Line: Experimental studies suggest that glucagon-like peptide (GLP-1) might have immunomodulating effects.These changes were attenuated by exendin-4, possibly through the suppression of p38 MAPK.These results suggest that exendin-4 might downregulate pro-inflammatory responses and reduce oxidative stress by suppressing MAPK signaling pathways in type 2 diabetes.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and Therapeutics The Chinese University of Hong Kong Shatin Hong Kong SAR China.

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.

No MeSH data available.


Related in: MedlinePlus