Glucose metabolism and beta-cell mass in adult offspring of rats protein and or energy restricted during the last week of pregnancy

An association between low birth weight and later impaired glucose toleranc e was recently demonstrated in several human populations. Although fetal ma lnutrition is probably involved, the biological bases of such a relationshi p are not yet clear, and animal studies on the matter are scarce. The prese nt study was aimed to identify, in adult (8-wk) female offspring, the effec ts of reduced protein and/or energy intake strictly limited to the last wee k of pregnancy. Thus we have tested three protocols of gestational malnutri tion: a low-protein isocaloric diet (5 instead of 15%), with pair feeding t o the mothers receiving the control diet; a restricted diet (50% of the con trol diet); and a low-protein restricted diet (50% of low-protein diet). On ly the low-protein diet protocols, independent of total energy intake, led to a lower birth weight. The adult offspring female rats in the three depri ved groups exhibited no decrease in body weight and no major impairment in glucose tolerance, glucose utilization, or glucose production (basal state and hyperinsulinemic clamp studies). However, pancreatic insulin content an d beta-cell mass were significantly decreased in the low-protein isocaloric diet group compared with the two energy-restricted groups. Such impairment of beta-cell mass development induced by protein deficiency limited to the last part of intrauterine life could represent a situation predisposing to impaired glucose tolerance.