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)
| Autor: | Xin-He Zhou, Wen-Wen Zheng, Chao Zheng, Liang-Xue Wang, Ying Hong, Si-Si Dong, Chun-Ying Li |
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| Rok vydání: | 2018 |
| Předmět: |
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 |
| Zdroj: | Medical Science Monitor Basic Research |
| ISSN: | 2325-4416 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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