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Taxifolin improves disorders of glucose metabolism and water-salt metabolism in kidney via PI3K/AKT signaling pathway in metabolic syndrome rats
- Source :
- Life Sciences. 263:118713
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Aims Our study was designed to explore the function and mechanism of taxifolin on glucose metabolism and water-salt metabolism in kidney with metabolic syndrome (MS) rats. Main methods Spontaneous hypertensive rats were induced by fructose to establish MS model. Systolic blood pressure (SBP) and homeostasis model assessment of insulin resistance (HOMA-IR) were measured after 7 weeks of continuous administration with taxifolin. Kidney injury indices and histopathological evaluation were done. The apoptosis rate of primary kidney cells was detected by flow cytometry. Insulin signaling pathway related proteins and renal glucose transport-related proteins were detected by western blotting. We assessed the effects of taxifolin on sodium water retention and renin-angiotensin-aldosterone system (RAAS) in MS rats. We examined not only changes in urine volume, osmotic pressure, urinary sodium and urinary chloride excretion, but also the effects on NA+/K+-ATPase and RAAS indicators. We also detected changes in inflammatory factors by immunohistochemical staining and immunofluorescence. In vitro experiment, high glucose and salt stimulated NRK-52E cells. By adding the PI3K inhibitor (wortmannin) to inhibit the PI3K, the effects of inhibiting the PI3K/AKT signaling pathway on glucose metabolism, water-sodium retention and inflammatory response were discussed. Key findings Taxifolin effectively reversed SBP, HOMA-IR, the kidney indices and abnormal histopathological changes induced by MS. Besides, taxifolin called back the protein associated with the downstream glucose metabolism pathway of PI3K/AKT. It also inhibited overactivation of RAAS and inflammatory response. In vitro experiments have demonstrated that the PI3K/AKT signaling pathway plays an important role in this process. Significance Taxifolin can improve homeostasis of glucose, inhibit overactivation of RAAS and reduce inflammatory response by PI3K/AKT signaling pathway.
- Subjects :
- Male
0301 basic medicine
Blood Pressure
Carbohydrate metabolism
Pharmacology
Kidney
Rats, Inbred WKY
030226 pharmacology & pharmacy
General Biochemistry, Genetics and Molecular Biology
Renin-Angiotensin System
Phosphatidylinositol 3-Kinases
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Insulin resistance
Rats, Inbred SHR
medicine
Animals
Insulin
Glucose homeostasis
Taxifolin
General Pharmacology, Toxicology and Pharmaceutics
Protein kinase B
PI3K/AKT/mTOR pathway
Metabolic Syndrome
Akt/PKB signaling pathway
Sodium
Water
General Medicine
Water-Electrolyte Balance
medicine.disease
Rats
Disease Models, Animal
Glucose
030104 developmental biology
medicine.anatomical_structure
chemistry
Quercetin
Insulin Resistance
Proto-Oncogene Proteins c-akt
Signal Transduction
Subjects
Details
- ISSN :
- 00243205
- Volume :
- 263
- Database :
- OpenAIRE
- Journal :
- Life Sciences
- Accession number :
- edsair.doi.dedup.....2249dfbd6c58311b753354b69b9ca48b