Protein-caloric food restriction affects insulin-like growth factor system in fetal Wistar rat
Protein-caloric food restriction affects insulin-like growth factor system in fetal Wistar rat
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DOI：
10.1210/en.2004-0665
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发表时间：
2005-03-01
期刊：
影响因子：
4.8
通讯作者：
Alvarez, C
中科院分区：
文献类型：
--
作者：
Martín, MA;Serradas, P;Alvarez, C
我们先前已经表明，蛋白质卡路里营养不良的妊娠大鼠(妊娠最后一周对照饮食的35%)在21.5天后显示出β细胞质量增加。这种改变与胰岛素血症和总胰腺胰岛素含量的增加有关，这种模式与报道的轻度糖尿病母亲的婴儿相似。在这项工作中，我们研究了营养不良的胎儿：1)胰岛素、生长激素和IGFS及其结合蛋白(IGFBPs)等生长因子的可获得性是否与这种变化有关；2)在体外IGFS对β细胞的有丝分裂反应。结果表明，母体营养不良增加了营养不良胎儿胰腺IGF-I表达和胰岛IGF-I受体含量，降低了肝脏IGF-I表达和血清IGF-I水平。与对照组相比，血清IGF-II无明显变化，营养不良的胰腺组织中IGF-II的表达减弱，肝脏中IGF-II的表达无明显变化。营养不良的胎儿血清IGFBP-1水平及肝脏和胰腺IGFBP-1的mRNA表达正常，而血清IGFBP-2的浓度和胰腺中IGFBP-2mRNA的丰度增加。最后，与对照组相比，营养不良的胎儿胰岛在体外对IGFS的促有丝分裂反应显著增加。总之，在营养不良的胎儿中，胰岛β细胞质量的增加可能与局部增加的胰腺IGF-I mRNA刺激复制的β细胞反应有关；这种作用可能被胰岛IGF-I受体含量增加和胰腺IGFBP-2基因表达增强或有利于。
We have previously shown that fetuses from protein-caloric undernourished pregnant rats (35% of control diet during the last week of pregnancy) at 21.5 d post coitum exhibit increased beta-cell mass. This alteration is correlated with increased insulinemia and total pancreatic insulin content, a pattern similar to that reported in infants of mild diabetic mothers. In this work, we investigated in undernourished fetuses: 1) whether availability of growth factors such as insulin, GH, and IGFs and their binding proteins (IGFBPs) could be implicated in this alteration, and 2) the beta-cell mitogenic response to IGFs in vitro. The results show that maternal undernutrition increases pancreatic IGF-I expression and islet IGF-I receptor content in undernourished fetuses, whereas hepatic IGF-I expression and serum IGF-I levels were decreased. No changes were observed in serum IGF-II, and its expression was diminished in undernourished pancreases and unchanged in the liver, compared with control fetuses. Serum levels and liver and pancreatic mRNA expression of IGFBP-1 were found to be normal in undernourished fetuses, whereas the serum concentration and abundance of IGFBP-2 mRNA in pancreas were increased. Finally, the beta-cell mitogenic response to IGFs in vitro was significantly increased in undernourished fetal islets, compared with controls. In conclusion, in undernourished fetuses the increased beta-cell mass can be related to the stimulation of replicative beta-cell response due to locally increased pancreatic IGF-I mRNA; this effect is perhaps potentiated or favored by the enhanced islet IGF-I receptor content and pancreatic IGFBP-2 gene expression.