Effects of sitagliptin and glucagon like peptide-1 on the regulations of genes involved in iron metabolism in human umbilical vein endothelial cells

Abstract

Objective To investigate the effects of sitagliptin and glucagon like peptide-1 (GLP-1) on the iron metabolism in human umbilical vein endothelial cells (HUVECs) under normal and high glucose conditions. Methods HUVECs were treated with sitagliptin (1 μmol/L) and/or GLP-1 (100 nmol/L) under normal (5.5 mmol/L) and high glucose (30.0 mmol/L) conditions, and the corresponding control groups were also included. Cell viability was evaluated. After treatment for 24 h in normal glucose and 48 h in high glucose, mRNA and protein expressions of frataxin (FXN) and aconitase1 (ACO1) were measured by real-time PCR and Western blotting, respectively. Multiple-group comparisons were performed using one-way variance analysis.The two groups were compared using the Bonferroni test (when the variance homogeneity test was performed) or the Dunnett T3 test (when the variance homogeneity test was not satisfied). Results (1) Comparing with the control group (assuming its expression level was 1) under normal glucose condition, cell viability had no significance among those groups treated with GLP-1, sitagliptin and the combinations of sitagliptin and GLP-1 (0.99±0.04, 1.07±0.08, 1.06±0.05, F=4.059, all P>0.05); mRNA expressions of FXN were significantly decreased by combinations of sitagliptin and GLP-1 administration (0.68±0.18, t=3.59, P 0.05). (2) Comparing with the control group (assuming its expression level was 1) under high glucose condition, mRNA expressions of FXN were significantly increased by combinations of sitagliptin and GLP-1 administration (1.75±0.26, t=-5.71, P<0.05), while mRNA expressions of ACO1 showed no much significance after treatment with sitagliptin and/or GLP-1. Conclusions Without affecting cell proliferation in normal state of endothelial conditions, sitagliptin and GLP-1 may affect the intracellular iron metabolism by regulating the expression of FXN and ACO1 in HUVECs in normal or hyperglycemic conditions. Key words: Sitagliptin; Glucagon like peptide-1; Frataxin; Aconitase1; Human umbilical vein endothelial cells