Astragalus polysaccharide improves insulin sensitivity in KKAy mice: regulation of PKB/GLUT4 signaling in skeletal muscle

J Ethnopharmacol. 2010 Jan 8;127(1):32-7. doi: 10.1016/j.jep.2009.09.055. Epub 2009 Oct 2.


Ethnopharmacological relevance: Astragalus polysaccharide (APS) is an important bioactive component of Astragalus membranaceus Bunge (Leguminosae) that has been used in traditional Chinese medicine for treating diabetes.

Aim of the study: To study the mechanisms by which APS ameliorates diabetes, we examined whether treatment with APS improves insulin sensitivity in insulin-resistant mice and whether this is associated with an improvement of dysregulated protein kinase B and glucose transporter 4 expressions in skeletal muscle.

Methods: APS (700 mg kg(-1)day(-1)) or vehicle was administered to 12-week-old diabetic KKAy and nondiabetic C57BL/6J mice for 8 weeks. Changes in body weight, blood glucose level, insulin resistance index, and oral glucose tolerance were routinely evaluated. The expressions of protein kinase B and glucose transporter 4 in skeletal muscle tissues were determined with Western blot.

Results: KKAy mice developed persistent hyperglycemia, impaired glucose tolerance and insulin resistance. Insulin-stimulated protein kinase B phosphorylation and glucose transporter 4 translocation were significantly decreased in KKAy compared to age-matched C57BL/6J mice. APS treatment ameliorated hyperglycemia and insulin resistance. Although the content of protein kinase B and glucose transporter 4 in KKAy skeletal muscle were not affected by APS, insulin-induced protein kinase B Ser-473 phosphorylation and glucose transporter 4 translocation in skeletal muscle were partially restored by APS treatment. In contrast, APS did not have any effect on C57BL/6J mice.

Conclusions: These results indicate that APS can regulate part of the insulin signaling in insulin-resistant skeletal muscle, and that APS could be a potential insulin sensitizer for the treatment of type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astragalus propinquus / chemistry*
  • Blood Glucose / analysis
  • Body Weight / drug effects
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use
  • Enzyme Activation / drug effects
  • Female
  • Glucose Transporter Type 4 / metabolism*
  • Hypoglycemic Agents / isolation & purification
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / pharmacology
  • Insulin Resistance*
  • Mice
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Phosphorylation / drug effects
  • Plant Roots / chemistry
  • Polysaccharides / isolation & purification
  • Polysaccharides / pharmacology
  • Polysaccharides / therapeutic use*
  • Protein Transport / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects


  • Blood Glucose
  • Drugs, Chinese Herbal
  • Glucose Transporter Type 4
  • Hypoglycemic Agents
  • Insulin
  • Polysaccharides
  • Slc2a4 protein, mouse
  • Proto-Oncogene Proteins c-akt