Astragalus polysaccharide reduces hepatic endoplasmic reticulum stress and restores glucose homeostasis in a diabetic KKAy mouse model.
OBJECTIVE
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 Ay gene (700 mg/kg-1/d-1, 8 weeks) and a high glucose-induced HepG2 cell model (200 microg/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 (GSK3beta), 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.


CONCLUSIONS
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.
Mao
Xian-qing
XQ
Department of Pathophysiology, Medical College of Wuhan University, Hubei Provincial Key Laboratory of Allergy and Immune-Related Diseases, Wuhan 430071, China.
Wu
Yong
Y
Wu
Ke
K
Liu
Ming
M
Zhang
Jing-fang
JF
Zou
Feng
F
Ou-Yang
Jing-ping
JP
D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry*; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011134:Polysaccharides / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D001786:Blood Glucose; D007328:Insulin; D011134:Polysaccharides