Effect of astragalus polysaccharide on insulin resistance in KKAy mice: alteration in PKB/GLUT4 signal transduction

Abstract

Astragalus polysaccharide (APS) has been shown to improve glycemic control by increasing insulin sensitivity in the skeletal muscle of type 2 diabetic rats. To investigate whether the effect of APS on glucose disposal is associated with the altered insulin signaling, APS (700mg/kg/day) or vehicle was administered to 12-week-old KKAy and C57BL/6J mice for 8 weeks. KKAy mice developed hyperglycemia, hyperinsulinemia, obesity and impaired oral glucose tolerance, which were alleviated by treatment with APS. While skeletal muscle protein kinase B (PKB) level from KKAy and C57BL/6J mice were similar, insulin stimulated serine473 phosphorylation of PKB protein content was 56% lower in KKAy than that in C57BL/6J mice. APS treatment increased serine473 phosphorylation of PKB in KKAy mice (1.4 fold) compared to control, which was associated with a 1.3 fold increase in plasma membrane glucose transporter 4 (GLUT-4) protein content. In contrast, APS have no effect on C57BL/6J mice. These results indicate that defect in insulin-stimulated PKB serine473 phosphorylation and plasma membrane GLUT-4 translocation in skeletal muscle may play important roles in the development of insulin resistance in KKAy mice. The glucoregulatory effects of APS were dependent of an elevated insulin-stimulated PKB serine473 phosphorylation and plasma membrane GLUT4 protein expression in KKAy mice. (This study is supported by National Natural Sciences Foundation of China grant 30370673)