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

Laboratoire de Physiopathologie de la Nutrition, Centre National de la Recherche Scientifique-ESA 7059, Université Paris 7/D. Diderot, 75251 Paris, France An association between low birth weight and later impaired glucose tolerance was recently demonstrated in several human populations. Although fetal malnutrition is probably involved, the biological bases of such a relationship are not yet clear, and animal studies on the matter are scarce. The present study was aimed to identify, in adult (8-wk) female offspring, the effects of reduced protein and/or energy intake strictly limited to the last week of pregnancy. Thus we have tested three protocols of gestational malnutrition: a low-protein isocaloric diet (5 instead of 15%), with pair feeding to the mothers receiving the control diet; a restricted diet (50% of the control diet); and a low-protein restricted diet (50% of low-protein diet). Only the low-protein diet protocols, independent of total energy intake, led to a lower birth weight. The adult offspring female rats in the three deprived 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 and -cell mass were significantly decreased in the low-protein isocaloric diet group compared with the two energy-restricted groups. Such impairment of -cell mass development induced by protein deficiency limited to the last part of intrauterine life could represent a situation predisposing to impaired glucose tolerance. fetal malnutrition; endocrine pancreas