Effect of maternal low-protein diet and taurine on the vulnerability of adult Wistar rat islets to cytokines.

AIMS/HYPOTHESIS: A maternal low-protein diet has been shown to induce an increased susceptibility of fetal islets to cytokines, but this effect can be avoided by maternal taurine supplementation. Here, we question whether these effects persist until adulthood in the offspring, despite the animal having a normal diet after weaning. METHODS: Pregnant Wistar rats received a diet of either 20% or 8% protein (control [C group] and recuperated [R group] respectively), which was or was not supplemented with taurine (control treated with taurine [CT group] and recuperated treated with taurine [RT group] respectively) during gestation and lactation. When the female offspring reached adulthood, an OGTT was performed. In a second stage, islets were isolated from these offspring, then pretreated or not with taurine, and subsequently treated with cytokines. RESULTS: Fasting glycaemia was higher (p<0.05) and insulinaemia was lower (p<0.01) in the R group than in the C group. Taurine supplementation decreased insulinaemia in the CT group and tended to increase it in the RT group. After the OGTT, glycaemia in R animals was not different from that in the C group, despite a blunted insulin response (p<0.05) which was restored by taurine. Supplementation in C-group mothers led to a weak glucose intolerance. In vitro, more apoptotic cells were observed in R islets after cytokines treatment (p<0.01). The addition of taurine to the culture medium in the R and C groups protected the islets from the cytokines (p<0.01). Maternal taurine supplementation decreased the sensitivity of islets in the RT group (p<0.01), but increased sensitivity in the CT group (p<0.01). CONCLUSIONS/INTERPRETATION: The increased vulnerability of islets to cytokines due to a restriction of protein during fetal development was still evident when the offspring reached adulthood. The low-protein diet also induced hyperglycaemia in the presence of lower insulinaemia. Taurine supplementation protected adult islets of the R group from cytokine toxicity and restored the insulinaemia. However, unnecessary supplementation of taurine could have detrimental effects.

Taurine supplementation to a low protein diet during foetal and early postnatal life restores a normal proliferation and apoptosis of rat pancreatic islets.

AIMS/HYPOTHESIS: In our previous studies a low protein diet (8% vs 20%) given during foetal and early postnatal life induced abnormal development of the endocrine pancreas; beta-cell mass and islet-cell proliferation were reduced while apoptosis was increased. Taurine, an important amino acid for development was also reduced in maternal and foetal plasma of protein deficient animals. In this study we aim to evaluate the role of taurine in the alterations observed in rats after a low protein diet. METHODS: Four groups of rats were given either a control, a low protein, or control and low protein diets with 2.5% taurine in the drinking water. Diets were given to gestating and lactating mothers and to their pups until day 30. Beta and endocrine cell masses were analysed as well as DNA synthesis and apoptosis after taurine supplementation in foetuses and pups. We also investigated insulin like growth factor-II (IGF-II), inducible nitric oxide synthase (iNOS), and Fas by immunohistochemistry. RESULTS: In foetuses and neonates nourished with a low protein diet, taurine supplementation restored normal DNA synthesis and apoptosis. This led to adequate beta and endocrine cell mass in pups. In islet cells, immunoreactivity was increased for IGF-II, reduced for Fas and unchanged for iNOS after taurine supplementation. CONCLUSION/INTERPRETATION: Taurine supplementation to a low protein diet in foetal and early postnatal life prevents the abnormal development of the endocrine pancreas. The mechanisms by which taurine acts on DNA synthesis and apoptosis rate of endocrine cells involve IGF-II, Fas regulation but not iNOS.

Intrauterine low protein diet increases fetal beta-cell sensitivity to NO and IL-1 beta: the protective role of taurine.

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.