Unité BFA (biologie fonctionnelle et adaptive), laboratoire B2PE (biologie et pathologie du pancréas endocrine), université Paris-Diderot, Sorbonne-Paris-Cité, UMR 8251 Centre national de la Recherche Scientifique, 75205 Paris, France.
Unité BFA (biologie fonctionnelle et adaptive), laboratoire B2PE (biologie et pathologie du pancréas endocrine), université Paris-Diderot, Sorbonne-Paris-Cité, UMR 8251 Centre national de la Recherche Scientifique, 75205 Paris, France.
Diabetes Metab. 2014 Nov;40(5):323-30. doi: 10.1016/j.diabet.2014.02.003. Epub 2014 Jun 16.
A substantial body of evidence suggests that an abnormal intra-uterine milieu elicited by maternal metabolic disturbances as diverse as malnutrition, placental insufficiency, diabetes and obesity may be able to programme susceptibility of the foetus to later develop chronic degenerative diseases such as obesity, hypertension, cardiovascular diseases and type 2 diabetes (T2D). As insulin-producing cells have been placed centre stage in the development of T2D, this review examines developmental programming of the beta-cell mass (BCM) in various rodent models of maternal protein restriction, calorie restriction, overnutrition and diabetes. The main message is that whatever the initial maternal insult (F0 generation) and whether alone or in combination, it gives rise to the same programmed BCM outcome in the daughter generation (F1). The altered BCM phenotype in F1 females prohibits normal BCM adaptation during pregnancy and, thus, diabetes (gestational diabetes) ensues. This gestational diabetes is then passed from one generation (F1) to the next (F2, F3 and so on). This review highlights a number of studies that have identified epigenetic mechanisms that may contribute to altered BCM development and beta-cell failure, as observed in diabetes. In addition to their role in instilling the programmed defect, these non-genomic mechanisms may also be involved in its intergenerational transmission.
大量证据表明，母体代谢紊乱（如营养不良、胎盘功能不全、糖尿病和肥胖）引起的异常宫内环境可能会使胎儿易患肥胖症、高血压、心血管疾病和 2 型糖尿病（T2D）等慢性退行性疾病。由于产生胰岛素的细胞在 T2D 的发展中处于中心地位，因此本综述检查了各种母体蛋白质限制、热量限制、营养过剩和糖尿病的啮齿动物模型中β细胞质量（BCM）的发育编程。主要信息是，无论最初的母体损伤（F0 代）是什么，无论是单独发生还是组合发生，都会在后代（F1）中产生相同的编程 BCM 结果。F1 雌性中改变的 BCM 表型阻止了怀孕期间正常的 BCM 适应，因此会导致糖尿病（妊娠糖尿病）。这种妊娠糖尿病会从一代（F1）传递到下一代（F2、F3 等）。本综述强调了一些研究，这些研究确定了表观遗传机制可能导致 BCM 发育和β细胞衰竭改变，如在糖尿病中观察到的那样。除了在灌输编程缺陷方面的作用外，这些非基因组机制也可能参与其跨代传递。
