An increased vulnerability of adult β-cells seems to be programmed in early life as adult islets from the progeny of dams fed a low-protein diet exhibited an increased apoptotic rate after cytokine stimulation. This was prevented by maternal taurine supplementation. Here, we investigated the mechanisms implicated in such an increased vulnerability and how taurine exerts its protective role. Throughout gestation and lactation, Wistar rats were fed a 20% (control (C group)) or an isocaloric 8% protein diet (recovery (R group)) supplemented or not with taurine (control+taurine and recovery+taurine groups respectively). Offspring received a 20% protein diet after weaning. Islets from 3-month-old females were isolated and cultured for 48 h before being incubated with or without cytokines for 24 h. In unstimulated islets, apoptotic rate and NO^. secretion were higher in R than in C. Both GADD153 mRNA and protein were increased, whereas mRNA of mitochondrial gene ATPase6 was downregulated in R group compared with C. In the RT group, taurine prevented apoptosis and restored a normal NO^. production in GADD153 as well as ATPase6 mRNA expression. After cytokines-induction, apoptosis and NO^. secretion were still increased in R compared with C but both parameters were normalized in the RT group. In conclusion, a maternal low-protein diet programmes a different pattern of gene expression in islet-cells of adult progeny. Higher NO^. production by these islets could be an important factor in the subsequent cell death. The prevention of these events by maternal taurine supplementation emphasizes the importance of taurine during endocrine pancreas development.

Abstract

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.

Journal of Endocrinology (1996) 151, 501–506

An isocaloric low-protein (LP) diet (8% instead of 20% in controls) given to dams during gestation reduces the fractional insulin release of stimulated fetal islets. The LP diet lowers the plasma concentration of taurine in both pregnant rats and their fetuses. This study reports the effect of taurine on the in vitro release of insulin from control and LP fetal islets. Direct stimulation with taurine, methionine or leucine increased the release of insulin from control islets. Nevertheless, no effect on LP islets was observed with either taurine or methionine. The release of insulin from LP islets was reduced with leucine. The in vitro addition of taurine (0. 3 or 3 mM) to the culture medium increased the release of insulin from the control islets in response to arginine or leucine, but it did not restore the reduced responsiveness of LP islets to these amino acids. When 2.5% taurine was added to the drinking water of control or LP dams (groups C+T and LP+T) throughout gestation, the concentration of taurine increased in the serum of dams and fetuses of both groups. The release of insulin from the LP+T fetuses was restored to control levels when stimulated with taurine, methionine, leucine or arginine. In conclusion, taurine stimulated control fetal islets in vitro, but failed to do so in LP islets. However, the addition of taurine to the diet of LP dams restored to normal the release of insulin from LP fetal islets, indicating the importance of taurine during development for a normal fetal beta cell function.

We have demonstrated earlier that a low-protein (8% protein) diet during gestation alters fetal beta-cell development. Here, we investigated the effect of a low-protein diet as compared with a control (20% protein) diet, during gestation, on the sensitivity of fetal beta-cells against nitric oxide (NO) or interleukin-1 beta (IL-1 beta), and assessed the protective effect of taurine in vitro and in vivo. Neoformed islets from control fetuses or fetuses of dams fed a low-protein diet (LP group) were incubated with taurine, methionine or beta-alanine and then exposed to sodium nitropruside (SNP), a NO donor, or to IL-1 beta. To understand the effect of taurine in vivo, LP or control pregnant rats received 2.5% of taurine in the drinking water. Mortality and rate of apoptosis were quantified by confocal microscopy. Without treatment, rate of apoptosis was greater in LP group islets than in control islets (1.38+/-0.18% compared with 0.66+/-0.21% respectively, P<0.05). Addition of SNP 100 microM showed an augmentation in cell death, which was greater in the LP than in the control group (17.88+/-0.69% compared with 11.89+/-0.44% respectively, P<0.01). LP islets were more sensitive than control islets to IL-1 beta. Taurine was protective against SNP and IL-1 beta in both the groups, methionine provided a less protective effect than taurine, and pretreatment with beta-alanine had no protective effect. Taurine supplementation of the maternal diet reduced the rate of apoptosis induced by IL-1 beta in control islets and suppressed that induced by IL-1 beta in LP islets. Our findings indicate that a low-protein diet during gestation augments the sensitivity of fetal islet cells to NO and IL-1 beta. However, through in vitro and in vivo experiments our studies indicate that such effects can be rescued using amino acids such as taurine.