Karnik Satyajit K, Chen Hainan, McLean Graeme W, Heit Jeremy J, Gu Xueying, Zhang Andrew Y, Fontaine Magali, Yen Michael H, Kim Seung K
Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
Science. 2007 Nov 2;318(5851):806-9. doi: 10.1126/science.1146812.
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 beta-cells that was accompanied by reduced islet levels of menin and its targets. Transgenic expression of menin in maternal beta-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 beta-cell proliferation. These results expand our understanding of mechanisms underlying diabetes pathogenesis and reveal potential targets for therapy in diabetes.
在怀孕期间,母体胰岛会生长以适应动态的生理需求,但在这种情况下调节适应性胰岛生长的机制却知之甚少。在这里,我们表明,曾被描述为内分泌肿瘤抑制因子和转录调节因子的蛋白质Menin,可控制怀孕小鼠的胰岛生长。怀孕刺激了母体胰岛β细胞的增殖,同时伴随着Menin及其靶标的胰岛水平降低。在母体β细胞中Menin的转基因表达可阻止胰岛扩张,并导致高血糖和葡萄糖耐量受损,这些都是妊娠糖尿病的标志性特征。催乳素是一种妊娠激素调节因子,可抑制胰岛Menin水平并刺激β细胞增殖。这些结果扩展了我们对糖尿病发病机制的理解,并揭示了糖尿病治疗的潜在靶点。