| First Author | Jin HM | Year | 2013 |
| Journal | Endocrinology | Volume | 154 |
| Issue | 11 | Pages | 4068-77 |
| PubMed ID | 24008345 | Mgi Jnum | J:203822 |
| Mgi Id | MGI:5528781 | Doi | 10.1210/en.2013-1115 |
| Citation | Jin HM, et al. (2013) Antioxidant N-acetylcysteine protects pancreatic beta-cells against aldosterone-induced oxidative stress and apoptosis in female db/db mice and insulin-producing MIN6 cells. Endocrinology 154(11):4068-77 |
| abstractText | Previous studies have shown that primary aldosteronism is associated with glucose-related metabolic disorders. However, the mechanisms by which aldosterone (ALDO) triggers beta-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 beta-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 beta-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 beta-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 beta-cell dysfunction and that NAC, but not SPL, may protect pancreatic beta-cells of mice from ALDO-induced oxidative stress and apoptosis in a manner independent of its receptor. |
