1. Phlorizin Exerts Direct Protective Effects on Palmitic Acid (PA)-Induced Endothelial Dysfunction by Activating the PI3K/AKT/eNOS Signaling Pathway and Increasing the Levels of Nitric Oxide (NO)
- Author
-
Xin-He Zhou, Wen-Wen Zheng, Chao Zheng, Liang-Xue Wang, Ying Hong, Si-Si Dong, and Chun-Ying Li
- Subjects
0301 basic medicine ,Endothelium ,Nitric Oxide Synthase Type III ,Phlorizin ,Palmitic Acid ,Medical Biochemistry ,030204 cardiovascular system & hematology ,Pharmacology ,Nitric Oxide ,Protective Agents ,Transfection ,Nitric oxide ,03 medical and health sciences ,chemistry.chemical_compound ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,Sodium-Glucose Transporter 1 ,Sodium-Glucose Transporter 2 ,Enos ,medicine ,Human Umbilical Vein Endothelial Cells ,Humans ,Lactase-Phlorizin Hydrolase ,Endothelial dysfunction ,Phosphorylation ,RNA, Small Interfering ,Protein kinase B ,PI3K/AKT/mTOR pathway ,biology ,Chemistry ,digestive, oral, and skin physiology ,Reproducibility of Results ,Endothelial Cells ,General Medicine ,medicine.disease ,biology.organism_classification ,030104 developmental biology ,medicine.anatomical_structure ,Phlorhizin ,Diabetes Mellitus, Type 2 ,Endothelium, Vascular ,Signal transduction ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
BACKGROUND Sodium glucose transporter-2 inhibitors are the newest antidiabetic drugs that seem to be cardioprotective and can prevent type 2 diabetes in patients with high cardiovascular risks. Previous clinical trials have shown that these inhibitors can alleviate endothelial dysfunction, but the mechanism of action remains unknown. How SGLT inhibitor influences the release of NO in PA-induced HUVECs has never been reported. MATERIAL AND METHODS To explore the potential effects of the endothelial-protective mechanism of phlorizin and its impact on nitric oxide (NO), human umbilical vein endothelial cells (HUVECs) were incubated with palmitic acid (PA) and then treated with phlorizin. Western blotting was performed to assess the phosphorylation of AKT, eNOS, and IRS-1. To further explore potential targets, siRNA transfection was used to demonstrate the role of SGLT1 and SGLT2. RESULTS Phlorizin suppressed the expression of SGLT1 and SGLT2, activated the PI3K/AKT/eNOS signaling pathway, increased the output of NO, and promoted the consumption of glucose in PA-induced HUVECs. Through demonstrating siRNA suppression of the expression of SGLT1 and SGLT2 in PA-induced HUVECs, this study provides a new understanding of the mechanism behind SGLT1 and SGLT2. CONCLUSIONS Our data demonstrate that phlorizin ameliorates the endothelial dysfunction link with the activation of the PI3K/AKT/eNOS signaling pathway and augmentation of the release of NO, partially through suppressing the expression of SGLT1 and SGLT2 in PA-induced HUVECS.
- Published
- 2018