Nicotinamide regulates blood glucose level and affects mitochondrial superoxide level in gestational diabetic rats

Abstract

Objective: To investigate the effects of nicotinamide (NAM) on blood glucose level and anti-oxidative enzyme activity in gestational diabetic (GDM) rats. Methods: GDM model was induced by injection of STZ (35 mg/kg) in pregnant female Sprague-Dawley rats. Nicotinamide was given to GDM rats by gavage at 50, 100 or 200 mg/kg q.d from gestational d 6 to d 20. The rats were divided into normal control group, GDM group (0 mg/kg), low-dose NAM group (50 mg/kg), middle-dose NAM group (100 mg/kg) and high-dose NAM group (200 mg/kg) with 8 animals in each group. When rats were sacrificed at d 21, the blood glucose level was measured; skeletal muscle and fetal brain samples were collected. The expression and activity of anti-oxidative enzymes, including superoxide dismutase (SOD1, SOD2), catalase (CAT) and sirtuin-3 (SIRT3) were measured by RT-PCR and Western blot. Results: Nicotinamide significantly lowered the blood glucose in GDM rats and decreased mitochondrial superoxide level in the fetal cortical neurons. SOD2 was induced in skeletal muscle by nicotinamide in GDM rats (P<0.05), while no significant change was observed in the expression of CAT (P>0.05). Nicotinamide increased SIRT3 expression (P<0.05) and decreased deacetylation of SOD2 in skeletal muscle of GDM rats (P<0.05). Conclusion: Nicotinamide can lower the blood glucose level in GDM rats, and decrease mitochondrial superoxide level, which is associated with promoting SIRT3 activity to deacetylate SOD2 and elevate SOD2 activity in GDM rats.