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 -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 -cells against nitric oxide (NO) or interleukin-1 (IL-1 ), and assessed the protective effect of taurine in vitro and in vivo. Neoformed islets from control fetuses or fetuses of dams fed a lowprotein diet (LP group) were incubated with taurine, methionine or -alanine and then exposed to sodium nitropruside (SNP), a NO donor, or to IL-1 . 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 µM 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 . Taurine was protective against SNP and IL-1 in both the groups, methionine provided a less protective effect than taurine, and pretreatment with -alanine had no protective effect. Taurine supplementation of the maternal diet reduced the rate of apoptosis induced by IL-1 in control islets and suppressed that induced by IL-1 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 . However, through in vitro and in vivo experiments our studies indicate that such effects can be rescued using amino acids such as taurine.

The intrauterine metabolic environment modulates the gene expression pattern in fetal rat islets: prevention by maternal taurine supplementation

“…Beta cells from LP fetuses feature an increased rate of apoptosis after exposure to interleukin 1β and nitric oxide [11]. This might be caused by reduction in expression of Hspa1a, Hspa1b, Hspb1 and Sod3 as observed in the microarray, Hspa1a being confirmed by RT-PCR.…”

“…IGF-2 exerts its mitogenic and antiapoptotic action via its binding to the IGF-1 receptor. IGF-1 receptor knockout mice have 50% reduction in their beta cell mass [40] and deletion of the IGF-1 and insulin receptors in the beta cell induced reduced beta cell mass and increased apoptosis and default in insulin secretion, three alterations that were also observed in the LP fetal islets [8,11,14].…”

“…A recent review study suggested that inadequate maternal nutrition might disturb the development of the fetus, which must adopt strategies to ensure survival that will programme its future health [3]. In experimental animal models, alteration of the intrauterine environment induced, for example, by gestational diabetes [4], placental insufficiency [5,6] or poor maternal nutrition [7][8][9][10][11] compromise the development of endocrine pancreas in the progeny and impact on its future health even in the subsequent generation [4,6,12]. Reduction of food intake by 50% in rats during gestation reduced the beta cell mass in offspring at birth by 30% [9].…”

“…Reduction of food intake by 50% in rats during gestation reduced the beta cell mass in offspring at birth by 30% [9]. When maternal diet was reduced in protein content during gestation, a number of findings were observed: reduction in beta cell mass due to diminished proliferation [8,13], enhanced apoptosis [11,13], reduced insulin secretion in vitro from isolated islets [14], impaired islet vascularisation [8,15] and enhanced sensitivity to cytotoxic effects of cytokines in vitro [11]. Increased susceptibility to cytokine cytotoxicity and lower insulin secretion persisted in adulthood despite limiting the low-protein (LP) diet to the period of gestation and lactation [7,12].…”

“…Taurine is important during development [17]. Supplementation of the maternal LP diet with taurine to normalise the fetal plasma level corrected pancreas development, the insulin secretory deficiency and susceptibility to cytokines and toxins [11,12,15,18,19].…”