Beta-cell mass and proliferation following late fetal and early postnatal malnutrition in the rat.
We have recently shown that maternal food restriction during late pregnancy in rats decreased beta-cell mass in the offspring at birth, without altering beta-cell proliferation. The aim of the present work was to determine: 1) whether sustained maternal undernutrition until weaning (R group) more dramatically alters beta-cell mass in the offspring and if normal food supply from weaning until adulthood could reverse the deleterious effects and; 2) if altered beta-cell proliferation was responsible for the decreased beta-cell mass. Beta-cell fraction and proliferative capacity were determined during the suckling period and at adult age after ad libitum feeding from weaning in the R animals and in age-matched controls (C group). At day 21, the offspring born and nursed by food-restricted mothers (R animals) showed a 66% reduction in beta-cell mass and number, which did not increase from birth to weaning, although beta-cell proliferation remained normal. At 3 months of age, R animals had 35% decreased beta-cell fraction, with a 50% decrease in the head of the pancreas. In that area, beta-cell proliferation was similar to that of the controls. In the tail of the pancreas, beta-cell fraction was only slightly impaired but beta-cell proliferation was increased by 37%, as compared with the controls. This increase was associated with a shift in islet size distribution towards medium and large islets compared with the head of pancreas from these R animals. No regional variations of beta-cell fraction, proliferation or islet size distribution were observed in adult control animals. In conclusion, prolonged malnutrition until weaning impairs beta-cell development but not beta-cell proliferation. Subsequent re-nutrition is followed by increased beta-cell proliferation but this is insufficient to fully restore beta-cell mass.
Garofano
A
A
INSERM U 457, Hôpital Robert Debré, Paris, France.
Czernichow
P
P
Bréant
B
B
D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division; D005260:Female; D005317:Fetal Growth Retardation / Q000473:pathology; D005508:Food Deprivation; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000254:growth & development / Q000473:pathology*; D010927:Placental Insufficiency / Q000473:pathology*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013217:Starvation / Q000473:pathology*
D007328:Insulin; D001973:Bromodeoxyuridine