Astragalus polysaccharide reduces hepatic endoplasmic reticulum stress and restores glucose homeostasis in a diabetic KKAy mouse model

作者：Mao Xian qing; Wu Yong; Wu Ke; Liu Ming; Zhang Jing fang; Zou Feng; Ou Yang Jing ping^*

来源：Acta Pharmacologica Sinica, 2007, 28(12): 1947-1956.

DOI：10.1111/j.1745-7254.2007.00674.x

• Astragalus membranaceus
• polysaccharide
• type 2 diabetes mellitus
• insulin resistance
• endoplasmic reticulum
• stress

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 hypogly-cemic 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 mu g/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 (GSK3 beta), an insulin signaling protein, was measured by Western blotting. Results: APS can alleviate ER stress in cultured cells in vivo. The hyperglycemia status, systemic insulin sensitivity, fatty liver disease, and insulin action in the liver of diabetic mice were partly normalized or improved in response to APS administration. 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.

• 出版日期2007-12
• 单位武汉大学; 荆楚理工学院