Insulin Sensitization and Anti‐obesity Effects of Astragalus Polysaccharide on High Fat Diet‐fed C57BL/6J Mice

Insulin resistance and obesity are two critical factors in type 2 diabetes (T2DM). We recently discovered a natural anti-diabetic substance, Astragalus polysaccharide (APS), which is a component of an aqueous extract of Astragalus membranaceus roots. Here we examine the underlying mechanism of the anti-diabetic action of APS. This study characterizes a insulin resistant mouse model treated with high-fat diet. Eight-week-old female C57BL/6J mice were fed a high fat diet (HFD) and treated with APS (700 mg/kg/day) for 12 weeks. Age and sex-matched, normal diet-fed controls were similarly treated. APS intervention significantly decreased the tendency of body weights to increase of HFD-fed C57BL/6J mice in weeks 8–12. After APS treatment, the HFD-fed mice showed a significant increase in insulin sensitivity. HFD-fed showed significantly increased levels and activities of PTP1B in skeletal muscle (1.7- and 1.9-fold, respectively) and liver (1.6- and 1.8-fold, respectively), thus diminishing insulin signaling in the target tissues. We found that the decreased insulin-stimulated GLUT4 translocation in muscles from insulin resistant mice were reversed after APS treatment. These effects were associated with significant decreases in high PTP1B levels and activities, respectively, in skeletal muscles and livers of APS treated mice. The non HFD diet-fed mice treated with APS did not significantly change PTP1B activities and levels, and blood insulin levels in normal diet-fed mice as well. These data suggest that APS enables insulin-sensitizing and anti-obesity effects at least in part by decreasing the elevated expression and activity of PTP1B in the skeletal muscles and livers from insulin resistant mice. (supported by NSFC grant No.30370673)