Anti-inflammatory effects of exendin-4, a glucagon-like peptide-1 analog, on human peripheral lymphocytes in patients with type 2 diabetes.
Anti-inflammatory effects of exendin-4, a glucagon-like peptide-1 analog, on human peripheral lymphocytes in patients with type 2 diabetes.
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Exendin-4（一种胰高血糖素样肽-1 类似物）对 2 型糖尿病患者的人外周淋巴细胞的抗炎作用。
DOI：
10.1111/jdi.12063
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发表时间：
2013-07-08
影响因子：
3.2
通讯作者：
Chan JC
中科院分区：
文献类型：
--
作者：
He L;Wong CK;Cheung KK;Yau HC;Fu A;Zhao HL;Leung KM;Kong AP;Wong GW;Chan PK;Xu G;Chan JC
2型糖尿病的特征是免疫功能失调、氧化应激和胰岛素效应降低。实验研究表明，胰升糖素样肽(GLP-1)可能具有免疫调节作用。我们假设GLP-1受体激动剂exendin-4可能减少2型糖尿病的炎症反应。用流式细胞术检测10例2型糖尿病患者和10例性别、年龄匹配的对照组外周血单个核细胞及PBMC培养上清液中磷酸化丝裂原活化蛋白激酶(MAPK)信号通路的表达。细胞因子/趋化因子和超氧阴离子浓度分别采用细胞微球阵列和化学发光法进行检测。与对照组相比，2型糖尿病患者外周血中MAPK(P38、c-jun氨基末端蛋白激酶和细胞外信号调节激酶)信号通路激活，超氧阴离子浓度升高，促炎细胞因子(肿瘤坏死因子-α、白介素1-β、白介素6)和趋化因子(CCL5/调节活化的正常T细胞表达和分泌及CXCL10/干扰素-γ诱导蛋白10)增加。这些变化可被exendin-4减弱，可能是通过抑制p38MAPK。这些结果表明，exendin-4可能通过抑制2型糖尿病的MAPK信号通路而下调促炎反应和减轻氧化应激。
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. 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. 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. 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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影响因子：
7.7
作者：
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