Protective effect of D-glucose, L-leucine and fetal calf serum against oxidative stress in neonatal pancreatic islets

B-cell destruction during the onset of diabetes mellitus is associated with oxidative stress. In this work, we investigated the mechanisms of defense against oxidative stress present in neonatal islets and their modulation by D-glucose, L-leucine and fetal calf serum (FCS). Culturing neonatal rat islets in the presence Of low D-glucose concentrations (2.8-5.6 mmol/l) and I mmol/l H2O2 increased the D-glucose uptake by islets sixfold compared to control levels. This effect was dose-dependently inhibited by D-glucose or FCS and by high concentrations of L-leucine. These supplements allowed islets to increase cytoplasmic catalase (CAT) activity only in response to H2O2, with no decrease in NO formation. Although L-leucine increased CAT activity and restored D-glucose uptake, it did not prevent damage to the islets. These data indicate that the most important H2O2 scavenger system in the islets is CAT and that this system can be modulated by metabolic substrates. (C) 2002 Elsevier Science B.V All rights reserved.