Effect of ageing on beta-cell mass and function in rats malnourished during the perinatal period

Aims/hypothesis. In a recently developed rat model, maternal food restricti on from day 15 of pregnancy until weaning induced low birth weight and a 70 % reduction of beta-cell mass in the offspring at day 21 after birth. Subs equent renutrition from weaning was insufficient to fully restore beta-cell mass in young adult rats. The aim of this study is to investigate the long -term consequences of early malnutrition on beta-cell mass and function. Methods. Oral glucose tolerance tests were done in 3- and 12-month-old anim als and beta-cell mass and apoptosis were determined by morphometrical meas urements on pancreatic sections. The specific impact of postnatal malnutrit ion was studied by comparing control animals (C group) with animals malnour ished during their fetal life only (R/C group), and animals malnourished du ring fetal life and until weaning (R group). Results. In 3-month-old R/C animals beta-cell mass reached 8.0 +/- 1.5 mg w ith no further increase until 12 months (8.1 +/- 1.5 mg), compared with 9.3 +/- 1.9 mg in control rats. Twelve-month-old R/C animals showed normal pla sma insulin responses and borderline glucose tolerance. In R animals, apopt osis reached 1.9 +/- 0.4% of the beta cells at 3 months, compared with 0.7 +/- 0.5 % in control rats, and beta-cell mass did not increase between 3 an d 12 months (4.7 +/- 0.8 mg at 12 months). In aged control and R animals, a poptosis affected 8% of the beta cells. At 12 months only, R animals showed profound insulinopenia and marked glucose intolerance. Conclusion/interpretation. In conclusion, perinatal malnutrition profoundly impairs the programming of beta-cell development. In animals with decrease d beta-cell mass the additional demand placed by ageing on the beta cells e ntails glucose intolerance since beta-cell mass does not expand and apoptos is is increased.