Boujendar Samira, Arany Edith, Hill David, Remacle Claude, Reusens Brigitte
Laboratoire de Biologie Cellulaire, World Health Collaborating Center for the Development of the Endocrine Pancreas, Université Catholique de Louvain, B-1348 Louvain-La-Neuve, Belgium.
J Nutr. 2003 Sep;133(9):2820-5. doi: 10.1093/jn/133.9.2820.
In rats, an isoenergetic low protein diet (LP) given throughout gestation perturbs the development of the endocrine pancreas by reducing beta-cell mass and islet vascularization at birth. Taurine, an important amino acid during development, has been found to be low in fetal and maternal plasma. When added to a LP diet, taurine normalizes beta-cell mass. Therefore, we investigated the ability of taurine to correct altered islet vascularization. Rats were given 20% [control (C)] or 8% (LP) protein in the diet with or without supplementation with 25 g/L taurine (T) in drinking water (C+T and LP+T) during gestation and lactation. Immunostaining for vascular endothelial growth factor (VEGF) and fetal liver kinase-1 (Flk-1), a VEGF receptor, was performed on fetal and neonatal pancreatic sections. Blood vessel density and blood vessel number were analyzed morphometrically on semi-thin sections. Taurine supplementation restored a normal volume and numerical density of vessels in fetal islets. The number of cells showing immunoreactivity for VEGF and Flk-1 was reduced by 33 and 45%, respectively, in islet cells from LP fetuses. In 1-mo-old pups, VEGF-positive cells remained decreased by nearly 22%. Both VEGF and Flk-1 were restored in pancreatic endocrine cells of fetuses and pups given taurine. The LP diet induced a threefold overexpression of Flk-1 in ductal cells, which contain precursors of beta cells. However, taurine supplementation was without effect. In conclusion, underexpression of VEGF and Flk-1 is associated with the lower fetal islet vascularization induced by the maternal malnutrition. The addition of taurine to the maternal diet prevents such damage and has a potential role in islet vasculogenesis.
在大鼠中,整个妊娠期给予等能量低蛋白饮食(LP)会通过减少出生时的β细胞量和胰岛血管形成来扰乱内分泌胰腺的发育。牛磺酸是发育过程中的一种重要氨基酸,已发现其在胎儿和母体血浆中的含量较低。当添加到LP饮食中时,牛磺酸可使β细胞量恢复正常。因此,我们研究了牛磺酸纠正胰岛血管形成改变的能力。在妊娠和哺乳期,给大鼠喂食含20%[对照(C)]或8%(LP)蛋白质的饮食,并在饮用水中添加或不添加25 g/L牛磺酸(T)(C+T和LP+T)。对胎儿和新生儿胰腺切片进行血管内皮生长因子(VEGF)和VEGF受体胎儿肝激酶-1(Flk-1)的免疫染色。在半薄切片上进行形态计量学分析血管密度和血管数量。补充牛磺酸可使胎儿胰岛中的血管体积和数量密度恢复正常。LP胎儿胰岛细胞中显示VEGF和Flk-1免疫反应性的细胞数量分别减少了33%和45%。在1月龄幼崽中,VEGF阳性细胞仍减少近22%。给予牛磺酸的胎儿和幼崽的胰腺内分泌细胞中VEGF和Flk-1均恢复正常。LP饮食诱导含有β细胞前体的导管细胞中Flk-1的表达增加了三倍。然而,补充牛磺酸没有效果。总之,VEGF和Flk-1的低表达与母体营养不良诱导的胎儿胰岛血管形成减少有关。在母体饮食中添加牛磺酸可预防这种损伤,并在胰岛血管生成中具有潜在作用。