美国斯坦福大学研究人员以实验鼠为对象进行的研究发现,怀孕实验鼠体内有一种蛋白质,会抑制与分泌胰岛素有关的细胞的生长,从而导致实验鼠出现妊娠糖尿病的典型症状。
斯坦福大学研究人员在2日出版的《科学》杂志上报告说,这种蛋白质名为menin,会在妊娠期出来“捣乱”,抑制胰腺贝塔细胞的生长,使胰岛素不能正常分泌,从而导致妊娠糖尿病的发生。
而在正常情况下,怀孕的时候,母体会分泌一种激素——促乳素,它能使menin蛋白质水平维持在低位,保证胰岛能制造足够的贝塔细胞,满足胰腺需求。这种自我调节能力可有效地防止妊娠糖尿病。
研究人员说,如果这一发现对人类也适用,那么这项研究有助于解释妊娠糖尿病这一常见妊娠并发症的发病机理。而且,研究人员有望在此基础上找到治疗妊娠糖尿病的新型药物疗法。
研究人员在小鼠身上发现了一个蛋白质,该蛋白质在妊娠期能抑制胰岛素生产细胞的产生,与妊娠糖尿病的主要特征有关。如果这一发现对人类也适用,这项研究也许能帮助解释这种常见的妊娠并发症,而且也许能提出新的药物治疗战略。
过去对小鼠和人类的研究曾发现妊娠期胰腺中所谓的beta细胞增殖,这使身体产生更多的胰岛素,以响应生长胚胎给母体增添的代谢需求。但是控制该增殖的分子机制在此之前一直不清楚,对增殖的控制帮助防止孕妇患妊娠糖尿病。
Satyajit Karnik 和同事通过研究小鼠模型和人类细胞,发现menin蛋白质在妊娠中抑制beta细胞的生长。与妊娠有关的激素催乳素(prolactin)看来维持胰岛中menin的低水平,胰岛是生产beta细胞的地方。这些结果表明,减少menin是身体刺激beta细胞增殖的一个自然的方法,menin或控制其活性的信号发生路径中的缺陷也许是妊娠糖尿病的原因之一。(新华网)
原始出处:
Science 2 November 2007:
Vol. 318. no. 5851, pp. 806 - 809
DOI: 10.1126/science.1146812
Menin Controls Growth of Pancreatic ß-Cells in Pregnant Mice and Promotes Gestational Diabetes Mellitus
Satyajit K. Karnik,1 Hainan Chen,1* Graeme W. McLean,1* Jeremy J. Heit,1* Xueying Gu,1 Andrew Y. Zhang,1 Magali Fontaine,2 Michael H. Yen,1,3 Seung K. Kim1,3
During pregnancy, maternal pancreatic islets grow to match dynamic physiological demands, but the mechanisms regulating adaptive islet growth in this setting are poorly understood. Here we show that menin, a protein previously characterized as an endocrine tumor suppressor and transcriptional regulator, controls islet growth in pregnant mice. Pregnancy stimulated proliferation of maternal pancreatic islet ß-cells that was accompanied by reduced islet levels of menin and its targets. Transgenic expression of menin in maternal ß-cells prevented islet expansion and led to hyperglycemia and impaired glucose tolerance, hallmark features of gestational diabetes. Prolactin, a hormonal regulator of pregnancy, repressed islet menin levels and stimulated ß-cell proliferation. These results expand our understanding of mechanisms underlying diabetes pathogenesis and reveal potential targets for therapy in diabetes.
1 Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
2 Department of Pathology, Stanford University, Stanford, CA 94305, USA.
3 Department of Medicine (Oncology Division), Stanford University, Stanford, CA 94305, USA.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: seungkim@stanford.edu