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Contrasted Impact of Maternal Rat Food Restriction on the Fetal Endocrine Pancreas¹

Instituto de Bioquímica (Centro Mixto Consejo Superior de Investigaciones Cientificas-Universidad Complutense de Madrid), Facultad de Farmacia, Ciudad Universitaria, 28040 Madrid, Spain; and Laboratoire de Physiopathologie de la Nutrition-Centre National de la Recherche Scientifique URA 307 (E.B., B.P.), F-75251 Paris Cedex 05, France

Address all correspondence and requests for reprints to: Dr. A. M. Pascual-Leone, Instituto de Bioquímica (Consejo Superior de Investigaciones Cientificas-Universidad Complutense de Madrid), Facultad de Farmacia, Ciudad Universitaria, 28040 Madrid, Spain. address: apascual{at}eucmvx.sim.ucm.es

The effects of food restriction of the mother (65% restriction of ad libitum food intake) on fetal and maternal insulin secretion and islet function were studied at 21 days gestation in three different rat populations: 1) undernourished from 0–7 days gestation, 2) undernourished from 7–14 days gestation, and 3) undernourished from 14–21 days gestation. The body weights of mothers were decreased in groups 2 and 3 vs. those in control fed pregnant animals, and no changes in basal parameters were found in any group. A glucose tolerance test in mothers from group 3 showed a mild intolerance to glucose and a decreased islet insulin content, although islet stimulation in vitro with glucose alone or plus arginine showed a normal insulin secretory response. Body weight was decreased in fetuses from the three groups (P < 0.01), and pancreas weight was reduced only in group 3. Insulinemia was increased in groups 2 and 3, and pancreatic insulin content increased only in group 3. However, fetuses from mothers of group 3 showed increased islet insulin content, increased response of insulin in vitro to glucose or glucose plus arginine, and hypertrophy of ß-cell mass. These results indicate, first, that the development of the fetal pancreas depends on a balanced maternal glucose homeostasis and, second, that adaptive maternal changes to undernutrition seem to induce alterations on the fetal endocrine pancreas, especially when food restriction is applied during the last week of gestation.

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