Age-dependent inability of the endocrine pancreas to adapt to pregnancy: Along-term consequence of perinatal malnutrition in the rat

We have recently shown that maternal food restriction during late pregnancy decreased beta-cell mass in the offspring at birth. Prolonged maternal mal nutrition until weaning led to irreversible decrease of beta-cell mass in t he adult male progeny. During pregnancy, the maternal endocrine pancreas de monstrates an acute and reversible increase in beta-cell mass. The aim of t his work was to investigate whether perinatal malnutrition could have long- lasting effects on glucose homeostasis and the adaptation of the endocrine pancreas to a subsequent pregnancy. This study was conducted on 4- and 8-mo nth-old female rats malnourished during their perinatal life and on age-mat ched control animals. Oral glucose tolerance tests (OGTT), pancreatic insul in content, and islet mass quantitation after dithizone staining were perfo rmed on the same animals. Four-month-old nonpregnant previously malnourishe d animals showed normal glucose tolerance but a significant decrease in ins ulin secretion during OGTT. These animals were, however, still able to adap t pancreatic insulin contents and doubled their islet mass in late gestatio n. At 8 months of age, insulin content before pregnancy was reduced to half that of controls. Moreover, it did not show the characteristic increase du ring gestation that could still be observed in pregnant control females. In those control animals, the islet mass increased regularly until late gesta tion (14.1 +/- 1.8 mg at day 20.5, vs. 9.8 +/- 1.2 mg, nonpregnant), wherea s in previously malnourished animals the islet mass remained throughout pre gnancy similar to the nonpregnant values (8.5 +/- 1.4 mg at day 20.5 us. 8. 9 +/- 3.6 mg, nonpregnant). In conclusion, early malnutrition has dramatic consequences on the capacity of the endocrine pancreas to meet the increase d insulin demand during pregnancy and aging.