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

Zhang, Lei, Zhang, Shi-Tao, Yin, Yan-Chun, Xing, Shu, Li, Wan-Nan, Fu, Xue-Qi
RSC advances 2018 v.8 no.27 pp. 14967-14974
animal disease models, blood glucose, blood serum, dipeptidyl-peptidase IV, dose response, glucagon-like peptide 1, glucose tolerance tests, glycemic effect, inhibitory concentration 50, insulin, insulin resistance, intestines, isoquercitrin, mice, noninsulin-dependent diabetes mellitus, oral administration
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 IC₅₀ and Kᵢ 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.