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. [Diabetologia (1998) 41: 1114–1120]
Keywords Beta cell - proliferation - rat - nutrition - immunohistochemistry - morphometry.
Received: 16 February 1998 and in revised form: 20 April 1998