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 preg nancy in rats decreased beta-cell mass in the offspring at birth, with out altering beta-cell proliferation. The aim of the present work was to determine: 1) whether sustained maternal undernutrition until weani ng (R group) more dramatically alters beta-cell mass in the offspring and if normal food supply from weaning until adulthood could reverse t he deleterious effects and; 2) if altered beta-cell proliferation was responsible for the decreased beta-cell mass. Beta-cell fraction and p roliferative capacity were determined during the suckling period and a t 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 i n beta-cell mass and number, which did not increase from birth to wean ing, although beta-cell proliferation remained normal. At 3 months of age, R animals had 35% decreased beta-cell fraction, with a 50% decrea se 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 conclusio n, prolonged malnutrition until weaning impairs beta-cell development but not beta-cell proliferation. Subsequent re-nutrition is followed b y increased beta-cell proliferation but this is insufficient to fully restore beta-cell mass.