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Hypoglycemic effect and mechanism of isoquercitrin as an inhibitor of dipeptidyl peptidase-4 in type 2 diabetic mice

机译:异槲皮苷作为二肽基肽酶-4抑制剂在2型糖尿病小鼠中的降血糖作用及其机制

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Glucagon-like peptide (GLP)-1 is a potent glucose-dependent insulinotropic gut hormone released from intestinal L cells. The aim of this study was to investigate isoquercitrin as an inhibitor of dipeptidyl peptidase IV (DPP-IV) and determine whether it affects GLP-1 release in normal mice and NCI-H716 cells. In vitro , we used chromogenic substrate method detection methods to measure DPP-IV. We found that isoquercitrin was a competitive inhibitor, with IC _(50) and K _(i) values of 96.8 and 236 μM, respectively. Isoquercitrin and sitagliptin also stimulated GLP-1 release in NCI-H716 cells. In vivo , a type 2 diabetic mouse model was established, and oral treatment with different concentration of isoquercitrin and sitagliptin for 8 weeks significantly decreased the fasting blood glucose level. The weight and the levels of serum GLP-1 and insulin of the mice in the isoquercitrin group were higher than those in the model group ( P < 0.001). An oral glucose tolerance test showed that the isoquercitrin significantly inhibited postprandial blood glucose changes in a dose-dependent manner. These findings demonstrated the hypoglycemic effects of isoquercitrin and indicated that isoquercitrin improved insulin sensitivity by targeting DPP-IV.
机译:胰高血糖素样肽(GLP)-1是从​​肠道L细胞释放的强效葡萄糖依赖性促胰岛素性肠激素。这项研究的目的是研究异槲皮苷作为二肽基肽酶IV(DPP-IV)的抑制剂,并确定其是否影响正常小鼠和NCI-H716细胞中GLP-1的释放。在体外,我们使用生色底物方法检测方法测量DPP-IV。我们发现异槲皮苷是一种竞争性抑制剂,IC _(50)和K _(i)值分别为96.8和236μM。异槲皮苷和西他列汀也刺激NCI-H716细胞中GLP-1的释放。在体内建立了2型糖尿病小鼠模型,用不同浓度的异槲皮苷和西他列汀口服治疗8周可显着降低空腹血糖水平。异槲皮苷组小鼠的体重和血清GLP-1和胰岛素水平高于模型组(P <0.001)。口服葡萄糖耐量试验表明,异槲皮苷以剂量依赖性方式显着抑制餐后血糖变化。这些发现证明了异槲皮苷的降血糖作用,并表明异槲皮苷通过靶向DPP-IV改善了胰岛素敏感性。

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