Astragalus polysaccharide reduces hepatic endoplasmic reticulum stress and restores glucose homeosta

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:shifujia
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Aim:To examine the potential effects of Astragalus polysaccharide (APS) onhepatic endoplasmic reticulum (ER) stress in vivo and in vitro and its link withhypoglycemia activity,thus establishing the mechanism underlying the hypogly-cemic action of APS.Methods:The obese and type 2 diabetic KKAy mousemodel,which is the yellow offspring of the KK mice expressed A~y gene (700mg·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 reflexinsulin sensitivity with the calculated homeostasis model assessment (HOMA-IR) index.XBP 1 (XhoI site-binding protein 1) transcription and splicing,an indica-tor of ER stress,was analyzed by RT-PCR and real-time PCR.The expression andactivation of glycogen synthase kinase 3 beta (GSK3β),an insulin signaling protein,was measured by Western blotting.Results:APS can alleviate ER stress in cul-tured cells in vivo.The hyperglycemia status,systemic insulin sensitivity,fattyliver disease,and insulin action in the liver of diabetic mice were partly normalizedor improved in response to APS administration.Conclusion:Our results indicatethat APS enables insulin-sensitizing and hypoglycemic activity at least in part byenhancing the adaptive capacity of the ER,which can further promote insulinsignal transduction.Thus,APS has promising application in the treatment of type2 diabetes. Aim:To examine the potential effects of Astragalus polysaccharide (APS) onhepatic endoplasmic reticulum (ER) stress in vivo and in vitro and its link withhypoglycemia 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 (700mg·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 reflexinsulin sensitivity with the calculated homeostasis model assessment (HOMA-IR) index.XBP 1 (XhoI site-binding protein 1) transcription and splicing,an Indica-tor 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 determined by Western blotting. Results: APS can alleviate ER stress In cul-tured cells in vivo.The hyperglycemia status,systemic insulin sensi Tivity,fattyliver disease,and insulin action in the liver of diabetic mice werepart normal normalized improved in response to APS administration.Conclusion:Our results indicatethat APS enabled insulin-sensitizing and hypoglycemic activity at least in part byenhancing the adaptive capacity of the ER,which Can further promote insulinsignal transduction.Thus,APS has promising application in the treatment of type2 diabetes.
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