Acta Pharmacologica Sinica 2007 December; 28 (12): 1947-1956; doi: 10.1111/j.1745-7254.2007.00674.x

Aim: To examine the potential effects of Astragalus polysaccharide (APS) on hepatic endoplasmic reticulum (ER) stress in vivo and in vitro and its link with hypoglycemia activity, thus establishing the mechanism underlying the hypoglycemic action of APS.

Methods: The obese and type 2 diabetic KKAy mouse model, which is the yellow offspring of the KK mice expressed A^y gene (700 mg·kg^-1·d^-1, 8 weeks) and a high glucose-induced HepG2 cell model (200 µg/mL, 24 h) were treated with APS. The oral glucose tolerance test was measured to reflex insulin sensitivity with the calculated homeostasis model assessment (HOMA-IR) index. XBP1 (XhoI site-binding protein 1) transcription and splicing, an indicator of ER stress, was analyzed by RT_PCR and real-time PCR. The expression and activation of glycogen synthase kinase 3 beta (GSK3β), an insulin signaling protein, was measured by Western blotting.

Results: All 4 types of integrins bound soluble fibrinogen in the absence of agonist stimulation, and only the cells expressing the chimeric α subunit with the wild-type β3 subunit, but not those with truncated β3, could adhere to and spread on immobilized fibrinogen.

Conclusion: Our results indicate that APS enables insulin-sensitizing and hypoglycemic activity at least in part by enhancing the adaptive capacity of the ER, which can further promote insulin signal transduction. Thus, APS has promising application in the treatment of type 2 diabetes.

Keywords: Astragalus membranaceus; polysaccharide; type 2 diabetes mellitus; insulin resistance; endoplasmic reticulum; stress