The present study investigated the anti-diabetic activity and potential mechanism of stigmasterol (SMR), which is a kind of phytosterols derived from the edible soybean oil in vitro and in vivo . SMR displayed a mild GLUT4 translocation activity by 1.44-fold in L6 cells. L6 cells were treated with different concentration of SMR, showing significant effects on the enhancing glucose uptake. SMR administrated orally to the KK-Ay mice significantly alleviated their insulin resistance and oral glucose tolerance with reducing fasting blood-glucose levels and blood lipid indexes such as triglyceride and cholesterol. Moreover, the GLUT4 expression in L6 cells, skeletal muscle and white adipose tissue had been also enhanced. In this paper we conclude that, stigmasterol seems to have potential beneficial effects on the treatment of type 2 diabetes mellitus with the probable mechanism of targeting GLUT4 glucose transporter included increasing GLUT4 translocation and expression.

The present study was undertaken to investigate the hypoglycemic activity and potential mechanisms of action of a flavonoid-rich extract from Sophora davidii (Franch.) Skeels (SD-FRE) through in vitro and in vivo studies. Four main flavonoids of SD-FRE namely apigenin, maackiain, leachianone A and leachianone B were purified and identified. In vitro, SD-FRE significantly promoted the translocation and expression of glucose transporter 4 (GLUT4) in L6 cells, which was significantly inhibited by Compound C (AMPK inhibitor), but not by Wortmannin (PI3K inhibitor) or Gö6983 (PKC inhibitor). These results indicated that SD-FRE enhanced GLUT4 expression and translocation to the plasma membrane via the AMPK pathway and finally resulted in an increase of glucose uptake. In vivo, using a spontaneously type 2 diabetic model, KK-Ay mice received intragastric administration of SD-FRE for 4 weeks. As a consequence, SD-FRE significantly alleviated the hyperglycemia, glucose intolerance, insulin resistance and hyperlipidemia in these mice. Hepatic steatosis, islet hypertrophy and larger adipocyte size were observed in KK-Ay mice. However, these pathological changes were effectively relieved by SD-FRE treatment. SD-FRE promoted GLUT4 expression and activated AMPK phosphorylation in insulin target tissues (muscle, adipose tissue and liver) of KK-Ay mice, thus facilitating glucose utilization to ameliorate insulin resistance. Regulation of ACC phosphorylation and PPARγ were also involved in the antidiabetic effects of SD-FRE. Taken together, these findings indicated that SD-FRE has the potential to alleviate type 2 diabetes.