Astragalus polysaccharide inhibits the expression and activity of hepatic Glycogen synthase kinase 3 (GSK‐3) in the type 2 diabetic KKAy mice model

• Published in: The FASEB journal 2006-03, Vol.20 (5), p.A1124-A1124
• Main Authors: MAO, Xian Qing, YANG, Jing Ping OU, WU, Ke, LIU, Min, WU, Yong
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.20.5.A1124-a

The deficient inhibitory control of GSK3 is an important factor in T2DM and that inhibitors of GSK3 could be therapeutically beneficial. To investigate the effect of Astragalus polysaccharide(APS), the polysaccharide component of the ethanol extract of astragalus roots, on hepatic GSK3 and its potential role in the amelioration of insulin resistance, twelve‐week old female KKAy mice(an animal model of T2DM)and C57BL/6J mice(the non‐diabetic mice controls)were respectively randomized into APS treated and untreated groups. The diabetic KKAy mice responded to 8‐week APS therapy with a significant decrease in the level of blood glucose, plasma insulin, body weight, the content of visceral fat and improved glucose tolerance by comprehensive analysis of Oral Glucose Tolerance Test (OGTT) and calculated HOMA‐IR index. In the stage of T2DM, the increases of gene transcription and protein expression/activity of hepatic GSK3 were measured by western blotting and RT‐PCR. In addition, the pathological features of the liver were presented through microscope and TEM. In this study we found the abnormalities of hepatic GSK3 and hepatic glycogen/TG/FFA returned to normal in APS treated KKAy mice. We also found typically hepatic steatosis in the KKAy mice which can be significantly alleviated with APS therapy. However, all the disturbances mentioned above did not occur in the two non‐diabetic control groups. These results indicate that GSK3 may be a new potential target for the treatment of T2DM. Furthermore, APS enables insulin‐sensitizing and can alleviate the extent of hepatic fatty degeneration, at least partly by inhibiting the expression and activity of the hepatic GSK3. This research is supported by National Nature Science Fund Of China(303705673).