Placental glycogen stores are increased in mice with H19 null mutations but not in those with insulin or IGF type 1 receptor mutations.
Placental glycogen stores are increased in mice with H19 null mutations but not in those with insulin or IGF type 1 receptor mutations.
复制标题
DOI：
10.1016/j.placenta.2009.05.004
复制
发表时间：
2009-08
期刊：
影响因子：
3.8
通讯作者：
Lopez MF
中科院分区：
文献类型：
--
作者：
Esquiliano DR;Guo W;Liang L;Dikkes P;Lopez MF
糖原在胎盘中的功能仍有争议。它是作为胎盘消耗的燃料来源，还是在胎儿需要的时候使用，还有待确定。两个印迹基因，胰岛素样生长因子2（Igf 2）和H19在胎盘中高度表达。我们以前已经证明，Igf 2缺乏的小鼠胎盘糖原水平较低。在这项研究中，我们使用H19基因（H19−/−）靶向破坏的小鼠来确定Igf 2过表达在胎盘生长和糖原储存中的重要性。此外，由于Igf 2通过胰岛素和/或IGF 1型受体介导其大部分功能，我们确定了这些受体的基因缺失是否会影响胎盘糖原储存。我们的数据表明，H19−/−小鼠的胎盘比H19+/+小鼠的胎盘更重，糖原细胞数量更多，糖原浓度也更高。GSK-3、ERK或总Akt表达或磷酸化在基因型之间没有差异;然而，H19−/−胎盘中Akt 1蛋白表达水平显著增加。从胰岛素受体或IGF 1型受体突变小鼠中获得的结果与其野生型同窝小鼠相比，胎盘糖原含量无差异，支持特异性胎盘Igf 2受体的概念。总之，这些结果支持Igf 2和Akt 1的作用，而不是胰岛素或IGF 1型受体，在胎盘生长和糖原代谢的调节。
The function of glycogen in the placenta remains controversial. Whether it is used as a source of fuel for placental consumption or by the fetus in times of need has yet to be determined. Two imprinted genes, insulin-like growth factor 2 (Igf2) and H19 are highly expressed in the placenta. We have previously demonstrated that mice with Igf2 deficiency have lower levels of placental glycogen. In this study, we used mice with targeted disruption of the H19 gene (H19−/−) to determine the importance of Igf2 overexpression in placental growth and glycogen stores. In addition, since Igf2 mediates most of its functions by signaling through the insulin and/or IGF Type 1 receptors, we determined whether gene deletions to these receptors could affect placental glycogen stores. Our data demonstrate that placentas from H19−/− mice are heavier, have higher number of glycogen cells, and contain larger glycogen concentrations than those of H19+/+ mice. No differences in GSK-3, ERK, or total Akt expression or phosphorylation were found between genotypes; however, Akt1 protein expression levels were significantly increased in H19−/− placentas. Results obtained from insulin receptor or IGF Type 1 receptor mutant mice did not show differences in placental glycogen content compared to their wild-type littermates, supporting the notion of a specific placental Igf2 receptor. Taken together, these results support a role for Igf2 and Akt1, but not the insulin nor the IGF Type 1 receptors, in the regulation of placental growth and glycogen metabolism.