L-leucine alters pancreatic β-cell differentiation and function via the mTor signaling pathway.
L-leucine alters pancreatic β-cell differentiation and function via the mTor signaling pathway.
复制标题
DOI：
10.2337/db11-0765
复制
发表时间：
2012-02
期刊：
影响因子：
7.7
通讯作者：
Scharfmann R
中科院分区：
文献类型：
--
作者：
Rachdi L;Aïello V;Duvillié B;Scharfmann R
亮氨酸(Leucine，Leu)是一种重要的支链氨基酸，可激活哺乳动物靶标雷帕霉素(MTOR)信号通路。Leu在胚胎发育过程中对细胞分化的影响尚不清楚。在这里，我们发现孕期补充亮氨酸显著增加胎儿体重，引起胎儿高血糖和低胰岛素血症，并减少相对胰岛面积。我们还利用大鼠胚胎胰腺组织块培养来阐明亮氨酸对β-细胞发育的作用机制。我们发现，在亮氨酸存在下，胰腺十二指肠同源盒-1阳性的祖细胞分化为神经生长素-3阳性的内分泌祖细胞效率低下，并导致β细胞的形成减少。在机制上，亮氨酸通过激活mTOR复合体1信号通路，增加细胞内缺氧诱导因子1-α的水平，这是胰腺内内分泌命运的抑制因子。总而言之，我们的研究结果表明，怀孕期间补充亮氨酸可能通过抑制胎儿生命易感期胰腺内分泌祖细胞的分化而潜在地增加2型糖尿病的风险。
Leucine (Leu) is an essential branched-chain amino acid, which activates the mammalian target of rapamycin (mTOR) signaling pathway. The effect of Leu on cell differentiation during embryonic development is unknown. Here, we show that Leu supplementation during pregnancy significantly increased fetal body weight, caused fetal hyperglycemia and hypoinsulinemia, and decreased the relative islet area. We also used rat embryonic pancreatic explant culture for elucidating the mechanism of Leu action on β-cell development. We found that in the presence of Leu, differentiation of pancreatic duodenal homeobox-1–positive progenitor cells into neurogenin3-positive endocrine progenitor cells was inefficient and resulted in decreased β-cell formation. Mechanistically, Leu increases the intracellular levels of hypoxia-inducible factor 1-α, a repressor of endocrine fate in the pancreas, by activating the mTOR complex 1 signaling pathway. Collectively, our findings indicate that Leu supplementation during pregnancy could potentially increase the risk of type 2 diabetes mellitus by inhibiting the differentiation of pancreatic endocrine progenitor cells during a susceptible period of fetal life.
登录
查看更多内容
影响因子：
64.8
作者：
JONSSON, J;CARLSSON, L;EDLUND, H
通讯作者：
EDLUND, H
DOI：
10.1084/jem.20081297
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen C;Liu Y;Liu R;Ikenoue T;Guan KL;Liu Y;Zheng P
通讯作者：
Zheng P
影响因子：
4.2
作者：
Layman, DK;Walker, DA
通讯作者：
Walker, DA
影响因子：
46.9
作者：
Kroon, Evert;Martinson, Laura A.;Baetge, Emmanuel E.
通讯作者：
Baetge, Emmanuel E.
影响因子：
14.8
作者：
Chen, Shuibing;Borowiak, Malgorzata;Melton, Douglas
通讯作者：
Melton, Douglas