APS decreased high glucose induced overexpression of PTP1B through inhibiting the activation of ATF6

Abstract

Protein tyrosine phosphatase 1B(PTP1B) which negatively regulated the insulin signaling was considered as a potential target to prevent and treat type 2 diabetes(T2DM). Endoplasmic reticulum(ER) stress was a key link between obesity, insulin resistance, and T2DM. Interestingly, PTP1B located on the cytosolic surface of ER and played an essential role in potentiating ER stress, we hypothesized that PTP1B may be a chaperon of ER stress. Activating transcription factor 6(ATF6) promoted the synthesis of chaperones when ER stress happened. We have found that astragalus polysaccharide(APS) could increase insulin sensitivity probably through decreasing the expression of PTP1B. In this study, we intended to investigate whether ATF6 was involved in this effect. Firstly, we used MTT assay to analyze the cytotoxicity of different concentration of APS and found that APS in a wide range had little cytotoxicity, approximately from 0‐1.6mg/ml; secondly, we used 25mmol/l D‐glucose to treat on cells for 24 hours, followed by APS with different concentrations mentioned above. Results showed that APS at 0.1‐0.8mg/ml decreased the expression of p50‐ATF6, APS at 0.2‐0.8mg/ml were more potential than 0.1mg/ml; while APS at 0.2‐0.8mg/ml reduced the expression of PTP1B and APS at 0.4mg/ml were more effective than 0.2 and 0.8mg/ml. So APS at 0.2‐0.8mg/ml may be the effective concentration range that can not only decrease the expression of PTP1B but also reduce glucose induced ER stress. This positive correlation provided significant information that APS decreased the expression of PTP1B was mediated at least partly through inhibiting the activation of ATF6.