Maternal antioxidants prevent β‐cell apoptosis and promote formation of dual hormone‐expressing endocrine cells in male offspring following fetal and neonatal nicotine exposure

Abstract

Fetal and neonatal nicotine exposure causes β-cell oxidative stress and apoptosis in neonates, leading to adult-onset dysglycemia. The aim of the present study was to determine whether an antioxidant intervention could prevent nicotine-induced β-cell loss. Nulliparous female Wistar rats received daily subcutaneous injections of either saline or nicotine bitartrate (1.0 mg/kg per day) for 2 weeks prior to mating until weaning. Nicotine-exposed dams received either normal chow or diet containing antioxidants (1000 IU/kg vitamin E, 0.25% w/w coenzyme Q10, and 0.1% w/w α-lipoic acid) during mating, pregnancy, and lactation; saline-exposed dams received normal chow. Pancreatic tissue was collected from male offspring at 3 weeks of age to measure β-cell fraction, apoptosis, proliferation, and the presence of cells coexpressing insulin and glucagon. The birth weight of offspring born to nicotine-exposed dams was significantly reduced in those receiving dietary antioxidants compared with those fed normal chow. Most interestingly, the antioxidant intervention to nicotine-exposed dams prevented the β-cell loss and apoptosis observed in nicotine-exposed male offspring whose mothers did not receive antioxidants. Male pups born to nicotine-treated mothers receiving antioxidants also had a tendency for increased β-cell proliferation and a significant increase in islets containing insulin/glucagon bihormonal cells compared with the other two treatment groups. The present study demonstrates that exposure to maternal antioxidants protects developing β-cells from the damaging effects of nicotine, thus preserving β-cell mass.