Antidiabetic activity of a Flavonoid-Rich extract from flowers of Wisteria sinensis in type 2 diabetic mice via activation of the IRS-1/PI3K/Akt/GLUT4 pathway

[Display omitted] •WS-FRE ameliorated a series of diabetes-related indices.•WS-FRE promoted GLUT4 translocation and expression by activating PI3K/Akt pathway.•WS-FRE ameliorated pathological changes of insulin-sensitive tissues.•WS-FRE regulated glucose metabolism through IRS-1/PI3K/Akt/GLUT4 pathway. The present study aimed to investigate anti-diabetic activities of a flavonoid-rich extract from Wisteria sinensis (WS-FRE). In vitro, WS-FRE significantly promote the translocation of GLUT4 (Glucose transporter 4) to the plasma membrane. Mechanisms analysis revealed that WS-FRE enhanced glucose uptake via activation of Akt and GLUT4. In vivo, 4-week treatment of WS-FRE alleviated the typical symptoms including hyperglycemia, glucose intolerance, hyperinsulinemia and dyslipidemia. Histopathological examinations revealed that WS-FRE relieved hepatic steatosis, adipocyte hypertrophy and pancreatic islet lesion to a certain extent in diabetic mice. Western blot analysis indicated that WS-FRE resulted in the suppression of IRS-1 serine phosphorylation and an elevation of PI3K p85, Akt phosphorylation and GLUT4 expression in insulin target tissues, which contributes to improving insulin sensitivity in peripheral tissues and thereby ameliorating glucose metabolism in diabetic mice. Diverse anti-diabetic effects of WS-FRE may be attributed to regulation of GLUT4, IRS-1 serine phosphorylation, PI3K phosphorylation and Akt phosphorylation.