HYPOGLYCEMIC EFFECT OF POLYSACCHARIDE ENRICHED EXTRACT OF ASTRAGALUS MEMBRANACEUS IN DIET INDUCED INSULIN RESISTANT C57BL/6J MICE AND ITS POTENTIAL MECHANISM

Abstract

To further confirm the hypoglycemic effect of APS and to investigate its possible mechanism. Diet‐induced insulin resistant C57BL/6J mice treated with or without APS (orally, 700 mg/kg/d) for 8 weeks were analyzed and compared. Simultaneously, an insulin resistant C2C12 cell model and an ER stressed HepG2 cell model were established and incubated with or without APS (200 μg/ml) for 24 hours respectively. Systematic insulin sensitivity was measured with an insulin‐tolerance test(ITT)and an homeostasis model assessment (HOMA IR) index. Metabolic stress variation was analyzed for biochemical parameters and pathological variations. The expression and activity of protein tyrosine phosphatase 1B (PTP1B) was measured by immunoprecipitation and Western blot. The ER stress response was analyzed through XBP1 transcription and splicing by real‐time PCR. APS could alleviate insulin resistance and ER stress induced by high glucose in vivo and in vitro respectively. APS enhanced adaptive capacity of the ER and promoted insulin signaling by the inhibition of the expression and activity of PTP1B. We have shown that APS has beneficial effects on insulin resistance and hyperglycemia. The mechanism is related to the alleviation of ER stress and insulin resistance under hyperglycemia conditions.