Silencing of DsbA-L gene impairs the PPARγ agonist function of improving insulin resistance in a high-glucose cell model.
- Author:
Xuan ZHOU
1
;
Jia-Qi LI
1
;
Li-Jie WEI
1
;
Meng-Zhou HE
1
;
Jing JIA
1
;
Jing-Yi ZHANG
1
;
Shao-Shuai WANG
1
;
Ling FENG
1
Author Information
- Publication Type:Journal Article
- Keywords: Disulfide-bond A oxidoreductase-like protein (DsbA-L); Peroxisome proliferator-activated receptor γ (PPARγ); Chemerin; Insulin signaling pathway; Gestational diabetes mellitus
- From: Journal of Zhejiang University. Science. B 2020;21(12):990-998
- CountryChina
- Language:English
- Abstract: Disulfide-bond A oxidoreductase-like protein (DsbA-L) is a molecular chaperone involved in the multimerization 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 receptor γ (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 PPARγ agonists 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 PPARγ agonists 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 PPARγ agonists 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 PPARγ agonists for raising insulin sensitivity. Overall, we further clarified the mechanism by which PPARγ agonists improve insulin resistance.
