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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).
- Source :
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Medical science monitor basic research [Med Sci Monit Basic Res] 2018 Jan 08; Vol. 24, pp. 1-9. Date of Electronic Publication: 2018 Jan 08. - Publication Year :
- 2018
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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.
- Subjects :
- Endothelium, Vascular drug effects
Human Umbilical Vein Endothelial Cells drug effects
Human Umbilical Vein Endothelial Cells metabolism
Humans
Phosphorylation drug effects
RNA, Small Interfering metabolism
Reproducibility of Results
Signal Transduction drug effects
Sodium-Glucose Transporter 1 metabolism
Sodium-Glucose Transporter 2 metabolism
Transfection
Endothelium, Vascular physiopathology
Nitric Oxide metabolism
Nitric Oxide Synthase Type III metabolism
Palmitic Acid toxicity
Phlorhizin pharmacology
Phosphatidylinositol 3-Kinases metabolism
Protective Agents pharmacology
Proto-Oncogene Proteins c-akt metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2325-4416
- Volume :
- 24
- Database :
- MEDLINE
- Journal :
- Medical science monitor basic research
- Publication Type :
- Academic Journal
- Accession number :
- 29307883
- Full Text :
- https://doi.org/10.12659/msmbr.907775