early low protein diet aggravates unbalance between antioxidant enzymes leading to islet dysfunction早期低蛋白质饮食加剧抗氧化酶之间的不平衡导致胰岛功能障碍.pdfVIP

Early Low Protein Diet Aggravates Unbalance between Antioxidant Enzymes Leading to Islet Dysfunction ´ Nicolas Theys, Andre Clippe, Thomas Bouckenooghe, Brigitte Reusens, Claude Remacle* ´ Laboratory of Cell Biology, Institute of Life Sciences, Universite catholique de Louvain, Louvain-la-Neuve, Belgium Abstract Background: Islets from adult rat possess weak antioxidant defense leading to unbalance between superoxide dismutase (SOD) and hydrogen peroxide-inactivating enzymatic activities, catalase (CAT) and glutathione peroxidase (GPX) rending them susceptible to oxidative stress. We have shown that this vulnerability is influenced by maternal diet during gestation and lactation. Methodology/Principal Findings: The present study investigated if low antioxidant activity in islets is already observed at birth and if maternal protein restriction influences the development of islet antioxidant defenses. Rats were fed a control diet (C group) or a low protein diet during gestation (LP) or until weaning (LPT), after which offspring received the control diet. We found that antioxidant enzymatic activities varied with age. At birth and after weaning, normal islets possessed an efficient GPX activity. However, the antioxidant capacity decreased thereafter increasing the potential vulnerability to oxidative stress. Maternal protein malnutrition changed the antioxidant enzymatic activities in islets of the progeny. At 3 months, SOD activity was increased in LP and LPT islets with no concomitant activation of CAT and GPX. This unbalance could lead to higher hydrogen peroxide production, which may concur to oxidative stress causing defective insulin gene expression due to modification of critical factors that modulate the insulin promoter. We found indeed that insulin mRNA