title: Antioxidant N-acetylcysteine protects pancreatic β-cells against aldosterone-induced oxidative stress and apoptosis in female db/db mice and insulin-producing MIN6 cells.
abstract: 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.
authors.affiliation: Division of Nephrology, Shanghai No. 3 People's Hospital, Shanghai Jiao Tong University School of Medicine, 280 Mo He Road, Shanghai 201900, China. panyu1980@163.com.
authors.forename: Hui Min
authors.initials: HM
authors.lastname: Jin
authors.forename: Dong Chi
authors.initials: DC
authors.lastname: Zhou
authors.forename: Hui Fang
authors.initials: HF
authors.lastname: Gu
authors.forename: Qing Yan
authors.initials: QY
authors.lastname: Qiao
authors.forename: Shun Kun
authors.initials: SK
authors.lastname: Fu
authors.forename: Xiao Li
authors.initials: XL
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Pan
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000450:Aldosterone / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight; D002460:Cell Line; D005260:Female; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011188:Potassium / Q000652:urine; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012964:Sodium / Q000652:urine
chemical_list: D001786:Blood Glucose; D007328:Insulin; D019253:Proto-Oncogene Proteins c-bcl-2; C052617:Bcl2 protein, mouse; D000450:Aldosterone; D012964:Sodium; D019255:NADPH Oxidases; D051057:Proto-Oncogene Proteins c-akt; D011188:Potassium; D000111:Acetylcysteine