Early low protein diet aggravates unbalance between antioxidant enzymes leading to islet dysfunction.
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.


RESULTS
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 level was reduced in both groups of malnourished offspring compared to controls. Analyzing the expression of such critical factors, we found that c-Myc expression was strongly increased in islets from both protein-restricted groups compared to controls.


CONCLUSIONS
Modification in antioxidant activity by maternal low protein diet could predispose to pancreatic islet dysfunction later in life and provide new insights to define a molecular mechanism responsible for intrauterine programming of endocrine pancreas.
Theys
Nicolas
N
Laboratory of Cell Biology, Institute of Life Sciences, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.
Clippe
André
A
Bouckenooghe
Thomas
T
Reusens
Brigitte
B
Remacle
Claude
C
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001835:Body Weight; D002374:Catalase / Q000378:metabolism; D004044:Dietary Proteins / Q000008:administration & dosage*; D004789:Enzyme Activation; D016259:Genes, myc; D005979:Glutathione Peroxidase / Q000378:metabolism; D007328:Insulin / Q000235:genetics; D007515:Islets of Langerhans / Q000201:enzymology / Q000378:metabolism*; D008098:Litter Size; D054464:Peroxiredoxins / Q000235:genetics; D051381:Rats
D000975:Antioxidants; D004044:Dietary Proteins; D007328:Insulin; D054464:Peroxiredoxins; D002374:Catalase; D005979:Glutathione Peroxidase