A low-protein diet (8 vs. 20%) administered during pregnancy affects the structure and function of the endocrine pancreas of the offspring. At 21.5 days of gestation, we reported a reduction of cell proliferation, islet size, islet vascularization, and pancreatic insulin content. In this study, we demonstrated an impairment of insulin secretion of these fetal islets when stimulated in vitro with amino acids such as arginine and leucine. If the offspring is kept on the same low-protein diet during suckling, weaning, and adulthood, fasting insulin levels remain low in the presence of normal blood glucose levels. Glucose tolerance at 70 days is impaired, with lower insulin response. In addition, permanent functional damage seems to be induced in utero by a low-protein diet, because a normal diet given from birth to adulthood does not restore normal insulin response after a glucose challenge. Our experimental results stress the impact of a balanced diet with qualitative and quantitative amino acid composition for the fetal endocrine pancreas to develop normally, without lasting functional and structural consequences in adulthood.

The localization of high-affinity uptake sites for 3H gamma-aminobutyric acid (3H-GABA) was investigated in the rat duodenum during ontogenesis and also at the adult stage (from 15.5 days of fetal life up to 105 days post natum) by means of low- and high-resolution autoradiography. At all stages studied, specific endocrine cell types of the epithelium were labelled and an intense uptake was detected in the nervous tissue, especially in glial cells but also in scarce neurones. When the incubation medium was supplemented with beta-alanine (1 mM), a blocker of the glial uptake for GABA, the labelling persisted only in endocrine cells and in few neurones. The intensity and the frequency of the labelling decreased at later periods compared to the earlier developmental stages. The GABA content of the duodenum as measured by a new ion-exchange column chromatography-HPLC-coupled method was higher in the early postnatal period compared to later stages. These observations suggest that GABA, in addition to being a neurotransmitter, may play an important role during development of the duodenum.

The influence of diabetic pregnancy on the fetal and newborn endocrine pancreas of rats was investigated in vitro and in vivo. A mild diabetic state was induced experimentally in the mother with 30 mg streptozotocin injected in the vein of the tail on the first day of gestation. The maternal blood sugar was 326 +/- 28 mg/dl at the end of the gestation. The in vitro experiment was performed on fetuses of 21.5 days. The endocrine pancreases were cultured during four or seven days and incubated the last 24 hours with tritiated thymidine. The healthy state of the islet cells after the two respective periods of culture was confirmed by an electron microscope study. After incubation with tritiated thymidine, a significantly higher percentage of labelled nuclei was observed in the islets of the diabetic group when compared with the controls. This was apparent after four days (diabetics: 54% - controls: 50%) and is obvious after seven days (diabetics: 28.8% - controls: 18%). For the in vivo experiment, two day old rats born at term from normal or diabetic mothers were injected (s.c.) with tritiated thymidine and killed two hours later. The proliferative capacity of the islet cells of pups born from diabetic mothers compared to the controls was higher when the percentage of labelled nuclei was calculated (respectively 5.4% versus 3.8%). An islet hypertrophy was also found in the diabetic group. In conclusion, our results combining in vitro techniques with in vivo observations demonstrate the higher proliferative rate of the fetal endocrine pancreas induced by a mildly diabetic feto-maternal environment.(ABSTRACT TRUNCATED AT 250 WORDS)

The localization of gamma-aminobutyric acid (GABA) high-affinity binding sites was investigated in the exocrine and endocrine pancreas of neonatal rats by means of 3H-GABA autoradiography. GABA-binding was identified on Schwann cells and on the cells of the intralobular excretory ducts. In the endocrine part of the pancreas, no labelling was observed except in peripheral islet cells which, on the basis of their scarcity and distribution, could be somatostatin cells. Furthermore, peri-insular innervation showed considerable labelling.

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