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

Abstract

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.