Disulfide-bond A oxidoreductase-like protein(DsbA-L)is a molecular chaperone involved in the multimeri-zation of adiponectin.Recent studies have found that DsbA-L is related to metabolic diseases including gestational...Disulfide-bond A oxidoreductase-like protein(DsbA-L)is a molecular chaperone involved in the multimeri-zation of adiponectin.Recent studies have found that DsbA-L is related to metabolic diseases including gestational diabetes mellitus(GDM),and can be regulated by peroxisome proliferator-activated receptorγ(PPARγ)agonists;the specific mechanism,however,is uncertain.Furthermore,the relationship between DsbA-L and the novel adipokine chemerin is also unclear.This article aims to investigate the role of DsbA-L in the improvement of insulin resistance by PPARγagonists in trophoblast cells cultured by the high-glucose simulation of GDM placenta.Immunohistochemistry and western blot were used to detect differences between GDM patients and normal pregnant women in DsbA-L expression in the adipose tissue.The western blot technique was performed to verify the relationship between PPARγagonists and DsbA-L,and to explore changes in key molecules of the insulin signaling pathway,as well as the effect of chemerin on DsbA-L.Results showed that DsbA-L was significantly downregulated in the adipose tissue of GDM patients.Both PPARγagonists and chemerin could upregulate the level of DsbA-L.Silencing DsbA-L affected the function of rosiglitazone to promote the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(PKB)/AKT pathway.Therefore,it is plausible to speculate that DsbA-L is essential in the environment of PPARγagonists for raising insulin sensitivity.Overall,we further clarified the mechanism by which PPARγagonists improve insulin resistance.展开更多
基金Project supported by the National Key Research and Development Program of China(Nos.2016YFC1000405 , 2018YFC1002903)。
文摘Disulfide-bond A oxidoreductase-like protein(DsbA-L)is a molecular chaperone involved in the multimeri-zation of adiponectin.Recent studies have found that DsbA-L is related to metabolic diseases including gestational diabetes mellitus(GDM),and can be regulated by peroxisome proliferator-activated receptorγ(PPARγ)agonists;the specific mechanism,however,is uncertain.Furthermore,the relationship between DsbA-L and the novel adipokine chemerin is also unclear.This article aims to investigate the role of DsbA-L in the improvement of insulin resistance by PPARγagonists in trophoblast cells cultured by the high-glucose simulation of GDM placenta.Immunohistochemistry and western blot were used to detect differences between GDM patients and normal pregnant women in DsbA-L expression in the adipose tissue.The western blot technique was performed to verify the relationship between PPARγagonists and DsbA-L,and to explore changes in key molecules of the insulin signaling pathway,as well as the effect of chemerin on DsbA-L.Results showed that DsbA-L was significantly downregulated in the adipose tissue of GDM patients.Both PPARγagonists and chemerin could upregulate the level of DsbA-L.Silencing DsbA-L affected the function of rosiglitazone to promote the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(PKB)/AKT pathway.Therefore,it is plausible to speculate that DsbA-L is essential in the environment of PPARγagonists for raising insulin sensitivity.Overall,we further clarified the mechanism by which PPARγagonists improve insulin resistance.
