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Background: 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. Methods: 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. Results: 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. Conclusion: The present study demonstrates that exposure to maternal antioxidants protects developing β-cells from the damaging effects of nicotine, thus preserving β-cell mass.

Background: Interventions that preserve or increase β-cell mass may also prevent Type 2 diabetes. Rosiglitazone alone, as well as in combination with metformin, prevents diabetes in people with high, yet non-diabetic glucose levels. These effects may be mediated through changes in β-cell mass. In the present study, the effect of combining rosiglitazone with metformin and/or insulin on β-cell mass and glucose levels was examined in a rat model of Type 2 diabetes. Methods: Diabetes-prone pups were randomized to receive rosiglitazone alone or in combination with metformin and/or insulin starting at 4 weeks of age. β-Cell mass and glucose homeostasis were examined in adulthood. Results: Rosiglitazone treatment reduced insulin resistance and partially restored β-cell mass in animals with reduced β-cell mass at birth. The addition of metformin to rosiglitazone decreased insulin resistance and reduced weight gain, but had no additional effect on β-cell mass. Conversely, the addition of insulin had no additional effect on these outcomes. Although the combination of rosiglitazone and metformin did not affect β-cell mass at 26 weeks of age, it did result in reduced body weight and insulin resistance. Conclusion: The results of the present study suggest that the addition of metformin to rosiglitazone improves the metabolic profile through an effect on insulin resistance and not β-cell mass.

Corticotrophin-releasing factor 2 receptor (CRF2R) agonists prevent muscle atrophy due to immobilization, denervation, and corticosteroid-induced muscle atrophy in wildtype mice. We hypothesized that a CRF2R agonist will increase skeletal muscle mass in mdx mice. Mdx (C57BL/10ScSn-Dmd(mdx)) and wildtype (C57BL/6) mice were divided into four groups: sedentary placebo, sedentary CRF2R agonist, exercised placebo, and exercised CRF2R agonist. Mice exercised on a treadmill twice weekly for 30 min (8-12 m/min, 8 weeks). Muscle and heart weights, serum creatine kinase, and gamma-glutamyltransferase activities were measured. The CRF2R agonist increased extensor digitorum longus and soleus muscle weights (P < 0.05) in wildtype and mdx mice. Sedentary mdx CRF2R and exercised mdx placebo mice had lower serum creatine kinase activity than sedentary mdx placebo mice. CRF2R-treated mice had decreased heart weights compared to placebo-treated mice. We conclude that CRF2R agonists should be further evaluated as a potential therapy for dystrophinopathies.

Reactive oxygen species (ROS) have been shown to modify proteins, lipids and DNA. These modified biomolecules serve as markers for the quantification of oxidative stress in various physiological an...