Open AccessAstragalus polysaccharide reduces hepatic endoplasmic reticulum stress and restores glucose homeostasis in a diabetic KKAy mouse model 1
Author(s) -
MAO Xianqing,
WU Yong,
WU Ke,
LIU Ming,
ZHANG Jingfang,
ZOU Feng,
OUYANG Jingping
Publication year - 2007
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2007.00674.x
Subject(s) - medicine , endocrinology , unfolded protein response , insulin , endoplasmic reticulum , xbp1 , glycogen synthase , glucose homeostasis , insulin resistance , homeostasis , type 2 diabetes , biology , glucose tolerance test , diabetes mellitus , microbiology and biotechnology , biochemistry , rna , rna splicing , gene
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 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 ( Xho I 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 : 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.