Antioxidant N-acetylcysteine protects pancreatic β-cells against aldosterone-induced oxidative stress and apoptosis in female db/db mice and insulin-producing MIN6 cells
| Autor: | Hui Min Jin, Qing Yan Qiao, Dong Chi Zhou, Yu Pan, Hui Fang Gu, Xiao Li Liu, Shun Kun Fu |
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| Rok vydání: | 2013 |
| Předmět: |
Blood Glucose
endocrine system medicine.medical_specialty medicine.medical_treatment Apoptosis Biology medicine.disease_cause Cell Line Acetylcysteine chemistry.chemical_compound Mice Endocrinology Mineralocorticoid receptor Mice Inbred NOD Internal medicine Insulin-Secreting Cells medicine Animals Insulin Receptor Aldosterone Body Weight Sodium NADPH Oxidases Oxidative Stress chemistry Proto-Oncogene Proteins c-bcl-2 Spironolactone Potassium Female Proto-Oncogene Proteins c-akt Oxidative stress medicine.drug |
| Zdroj: | Endocrinology. 154(11) |
| ISSN: | 1945-7170 |
| Popis: | Previous studies have shown that primary aldosteronism is associated with glucose-related metabolic disorders. However, the mechanisms by which aldosterone (ALDO) triggers β-cell dysfunction remains unclear. This study aimed to investigate whether oxidative stress is involved in and whether the antioxidant N-acetylcysteine (NAC) or the mineralocorticoid receptor antagonist spironolactone (SPL) could prevent or delay β-cell damage in vivo and in vitro. As expected, 8 weeks after ALDO treatment, 12-week-old female diabetic db/db mice exhibited impaired oral glucose tolerance, decreased β-cell mass, and heightened levels of oxidative stress marker (urinary 8-hydroxy-2′-deoxyguanosine). NAC reversed these symptoms completely, whereas SPL treatment did so only partially. After exposure to ALDO, the mouse pancreatic β-cell line MIN6 exhibited decreased viability and increased caspase-3 activity, as well as reduced expression of Bcl-2/Bax and p-AKT, even if mineralocorticoid receptor was completely suppressed with small interfering RNA. NAC, but not SPL, suppressed oxidative stress in MIN6 cells, as revealed by the decrease in inducible NOS levels and expression of the proteins p22-phox and p67-phox. These findings suggest that oxidative stress may be involved in ALDO-induced β-cell dysfunction and that NAC, but not SPL, may protect pancreatic β-cells of mice from ALDO-induced oxidative stress and apoptosis in a manner independent of its receptor. |
| Databáze: | OpenAIRE |
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