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.

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Islets of rat fetuses born to mothers fed a low protein diet (LP) have a depressed insulin secretion in vitro in response to secretagogues. These fetuses have lower plasma levels of taurine than controls. The aim of this study was to analyze the effect of taurine on fetal islets insulin secretion. After 5 days of culture in serum containing standard RPMI medium, islets were cultured for 2 days in serum-free DME/F12 medium with 8.2 or 16.7 mM glucose alone or with taurine at 0.3 or 3 mM. They were then incubated for 120 min in Krebs Ringer solution with glucose alone (5.6 or 16.7 mM) or glucose (5.6 mM) added to leucine or arginine (both at 10 mM). In both concentrations of glucose, taurine increased the fractional insulin release by islets stimulated with secretagogues tested during the incubation. The effect did not seem to be mediated by changes in cAMP content. In a second set of experiments, islets cultured in RPMI medium for 7 days were incubated in the presence of Krebs Ringer solution with leucine (10 mM) or with sulfur amino acids (taurine at 10 mM, methionine or cysteine at 5 mM) for 120 min. Taurine and methionine stimulated insulin release at the same magnitude as leucine, whereas cysteine had no effect. In conclusion, taurine enhances insulin secretion by fetal islets, at least in vitro. Low taurine levels in fetuses from LP mothers might be implicated in their depressed insulin secretion.

In rats that received a low protein isocaloric diet (protein content of the diet: 8 instead of 20%) during fetal life and thereafter up to the time of sacrifice at 12-13 weeks of age, a low plasma insulin concentration, a decreased insulin content of isolated pancreatic islets, and an impaired secretory response of the islets to either D-glucose or the association of L-leucine and L-glutamine coincided, in islet homogenates, with a low activity of the mitochondrial glycerophosphate dehydrogenase and an abnormally high ratio between glutamate-alanine and glutamate-aspartate transaminase activities. Opposite enzymatic changes were found in liver extracts of the same rats. No obvious change in these hormonal, secretory, and enzymatic variables were observed when the period of protein deficiency was restricted to fetal life. These findings support the view that, in protein malnutrition, an impaired activity of pancreatic B-cell mitochondrial glycerophosphate dehydrogenase contributes, possibly in association with other enzymatic anomalies, to the perturbation of islet function.

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The pancreatic islet blood flow and insulin secretion of adult rats submitted to an isocaloric low protein diet (8% vs. 20%) during pre- and postnatal life were investigated by the nonradioactive microsphere technique. In the basal state, female rats chronically exposed to a low protein diet (LP) displayed a specific marked decrease in islet blood flow (10 +/- 2 vs. 29 +/- 5 microliters/min.g pancreas; P < 0.01) and overall pancreatic blood flow (P < 0.01). The plasma insulin level, however, was not affected. During a glucose challenge, the control animals enhanced their islet blood flow 2.3-fold, whereas the LP group reached control values with a 6-fold increase. Plasma insulin levels rose similarly in the control and LP animals. A third group of animals designated the recuperation group, exposed to a low protein diet only in utero, displayed islet blood flow comparable to control values, but increased basal plasma insulin (2.0 +/- 0.3 vs. 1.2 +/- 0.1 ng/ml; P < 0.05). These data are consistent with the possibility of dissociation of islet blood flow and insulin release under basal conditions, which may not be the case after a glucose challenge. Furthermore, the low blood flow values in the LP group may reflect an adaptive physiological response, an impaired pancreatic vasculogenesis, or a dysfunction of endothelial cells.

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