Simmons Rebecca A
Department of Pediatrics, Children's Hospital, Philadelphia, PA, USA.
Pediatr Clin North Am. 2009 Jun;56(3):449-66, Table of Contents. doi: 10.1016/j.pcl.2009.03.004.
Intrauterine growth retardation (IUGR) has been linked to development of type 2 diabetes in adulthood. Using a rat model, we tested the hypothesis that uteroplacental insufficiency disrupts the function of the electron transport chain in the fetal beta-cell and leads to a debilitating cascade of events. The net result is progressive loss of beta-cell function and eventual development of type 2 diabetes in the adult. Studies in the IUGR rat demonstrate that an abnormal intrauterine environment induces epigenetic modifications of key genes regulating beta-cell development; experiments directly link chromatin remodeling with suppression of transcription. Future research will be directed at elucidating the mechanisms underlying epigenetic modifications in offspring.
宫内生长受限（IUGR）与成年后患2型糖尿病有关。我们使用大鼠模型检验了以下假设：子宫胎盘功能不全破坏了胎儿β细胞中电子传递链的功能，并导致一系列使人衰弱的事件。最终结果是β细胞功能逐渐丧失，成年后最终发展为2型糖尿病。对IUGR大鼠的研究表明，异常的子宫内环境会诱导调节β细胞发育的关键基因发生表观遗传修饰；实验直接将染色质重塑与转录抑制联系起来。未来的研究将致力于阐明后代表观遗传修饰的潜在机制。
