Zhang Lei, Zhang Shi-Tao, Yin Yan-Chun, Xing Shu, Li Wan-Nan, Fu Xue-Qi
Edmond H. Fischer Signal Transduction Laboratory, School of Life Sciences, Jilin University Changchun 130012 China.
College of Life Science and Technology, Mudanjiang Normal University Mudanjiang 157011 China.
RSC Adv. 2018 Apr 19;8(27):14967-14974. doi: 10.1039/c8ra00675j. eCollection 2018 Apr 18.
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. , we used chromogenic substrate method detection methods to measure DPP-IV. We found that isoquercitrin was a competitive inhibitor, with IC and values of 96.8 and 236 μM, respectively. Isoquercitrin and sitagliptin also stimulated GLP-1 release in NCI-H716 cells. , 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 ( < 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.
胰高血糖素样肽（GLP）-1是一种从肠道L细胞释放的强效葡萄糖依赖性促胰岛素肠道激素。本研究的目的是研究异槲皮苷作为二肽基肽酶IV（DPP-IV）抑制剂的作用，并确定其是否影响正常小鼠和NCI-H716细胞中GLP-1的释放。我们采用发色底物法检测方法来测定DPP-IV。我们发现异槲皮苷是一种竞争性抑制剂，其IC和 值分别为96.8和236μM。异槲皮苷和西他列汀也能刺激NCI-H716细胞中GLP-1的释放。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周可显著降低空腹血糖水平。异槲皮苷组小鼠的体重、血清GLP-1和胰岛素水平均高于模型组（<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著抑制餐后血糖变化。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改善胰岛素敏感性。
