美國斯坦福大學(xué)研究人員以實(shí)驗(yàn)鼠為對(duì)象進(jìn)行的研究發(fā)現(xiàn),，懷孕實(shí)驗(yàn)鼠體內(nèi)有一種蛋白質(zhì)，會(huì)抑制與分泌胰島素有關(guān)的細(xì)胞的生長,，從而導(dǎo)致實(shí)驗(yàn)鼠出現(xiàn)妊娠糖尿病的典型癥狀,。
斯坦福大學(xué)研究人員在２日出版的《科學(xué)》雜志上報(bào)告說，這種蛋白質(zhì)名為ｍｅｎｉｎ,，會(huì)在妊娠期出來“搗亂”,，抑制胰腺貝塔細(xì)胞的生長，使胰島素不能正常分泌,，從而導(dǎo)致妊娠糖尿病的發(fā)生,。
而在正常情況下，懷孕的時(shí)候,，母體會(huì)分泌一種激素——促乳素,，它能使ｍｅｎｉｎ蛋白質(zhì)水平維持在低位，保證胰島能制造足夠的貝塔細(xì)胞,，滿足胰腺需求,。這種自我調(diào)節(jié)能力可有效地防止妊娠糖尿病。
研究人員說,，如果這一發(fā)現(xiàn)對(duì)人類也適用,，那么這項(xiàng)研究有助于解釋妊娠糖尿病這一常見妊娠并發(fā)癥的發(fā)病機(jī)理。而且,，研究人員有望在此基礎(chǔ)上找到治療妊娠糖尿病的新型藥物療法,。
研究人員在小鼠身上發(fā)現(xiàn)了一個(gè)蛋白質(zhì),，該蛋白質(zhì)在妊娠期能抑制胰島素生產(chǎn)細(xì)胞的產(chǎn)生，與妊娠糖尿病的主要特征有關(guān),。如果這一發(fā)現(xiàn)對(duì)人類也適用,，這項(xiàng)研究也許能幫助解釋這種常見的妊娠并發(fā)癥，而且也許能提出新的藥物治療戰(zhàn)略,。
過去對(duì)小鼠和人類的研究曾發(fā)現(xiàn)妊娠期胰腺中所謂的beta細(xì)胞增殖,，這使身體產(chǎn)生更多的胰島素，以響應(yīng)生長胚胎給母體增添的代謝需求,。但是控制該增殖的分子機(jī)制在此之前一直不清楚,，對(duì)增殖的控制幫助防止孕婦患妊娠糖尿病。
Satyajit Karnik 和同事通過研究小鼠模型和人類細(xì)胞,，發(fā)現(xiàn)menin蛋白質(zhì)在妊娠中抑制beta細(xì)胞的生長,。與妊娠有關(guān)的激素催乳素(prolactin)看來維持胰島中menin的低水平，胰島是生產(chǎn)beta細(xì)胞的地方,。這些結(jié)果表明,，減少menin是身體刺激beta細(xì)胞增殖的一個(gè)自然的方法，menin或控制其活性的信號(hào)發(fā)生路徑中的缺陷也許是妊娠糖尿病的原因之一,。（新華網(wǎng)）
原始出處:
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: [email protected]
