The Activation of Peroxisome Proliferator-activated Receptor γ Enhances Insulin Signaling Pathways Via Up-regulating Chemerin Expression in High Glucose Treated HTR-8/SVneo Cells

Abstract

Abstract. Objective:. To investigate whether peroxisome proliferator-activated receptor γ (PPARγ) agonists, rosiglitazone and GW1929, activate the phosphatidylinositol 3-kinase (PI3K)-AKT/protein kinase B pathway and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase1/2 (ERK1/2) pathway by upgrading the expression of chemerin. Methods:. The HTR-8/SVneo trophoblastic cells were cultured in vitro in high glucose concentration (25 mmol/L) to mimic gestational diabetic phenotypes. We transfected small interfering RNA into HTR-8/SVneo cells to silence two receptors of chemerin, that are chemokine-like receptor 1 (CMKLR1) and G protein-coupled receptor1 (GPR1). And recombinant human chemerin, PPARγ agonists (rosiglitazone, 10 μmol/L and GW1929, 10 μmol/L) and PPARγ inhibitor (GW9662, 5 μmol/L) were additionally added to the medium, respectively. The existence of chemerin was verified by immunocytochemistry, and the expressions of PPARγ, chemerin, and its receptors as well as insulin signaling-related factors PI3K, AKT2, and MAPK (ERK1/2) were detected by real time quantitative-polymerase chain reaction and western blot. Results:. Chemerin existed in the HTR-8/SVneo cells. Effects of chemerin on PI3K-AKT pathway and MAPK (ERK1/2) pathway were dependent on the density of chemerin. When rosiglitazone and GW1929 were added to the medium, the mRNA levels of PI3K, AKT2, and MAPK1 were upregulated (P 0.05). Meanwhile, the expression of phospho-ERK2 remained unaffected in the absence of GPR1 (P > 0.05). Conclusion:. Both rosiglitazone and GW1929 have the effect of improving insulin signaling pathways via upgrading the level of chemerin in high glucose treated HTR-8/SVneo cells.