Division of Reproductive and Perinatal Research, Department of Obstetrics, Gynecology, and Women's Health, University of Missouri, Columbia, Missouri, USA.
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas, USA.
Biol Reprod. 2017 Feb 1;96(2):435-445. doi: 10.1095/biolreprod.116.144543.
Gestational diabetes mellitus (GDM) is a common obstetric complication. Half of women who have GDM will go on to develop type 2 diabetes. Understanding the mechanisms by which this occurs requires an animal model of GDM without ongoing diabetes at conception. C57Bl/6J mice react acutely to a high-fat, high-sucrose (HFHS) challenge. Here, we hypothesized that a periconceptional HFHS challenge will induce glucose intolerance during gestation. C57Bl/6J female mice were placed on an HFHS either 1 or 3 weeks prior to mating and throughout pregnancy. Intraperitoneal glucose tolerance tests, insulin measurements, and histological analysis of pancreatic islets were used to assess the impact of acute HFHS. C57Bl/6J females fed HFHS beginning 1 week prior to pregnancy became severely glucose intolerant, with reduced insulin response to glucose, and decreased pancreatic islet expansion during pregnancy compared to control mice. These GDM characteristics did not occur when the HFHS diet was started 3 weeks prior to mating, suggesting the importance of acute metabolic stress. Additionally, HFHS feeding resulted in only mild insulin resistance in nonpregnant females. When the diet was discontinued at parturition, symptoms resolved within 3 weeks. However, mice that experienced glucose intolerance in pregnancy became glucose intolerant more readily in response to a HFHS challenge later in life than congenic females that experienced a normal pregnancy, or that were fed the same diet outside of pregnancy. Thus, acute HFHS challenge in C57Bl/6 mice results in a novel, nonobese, animal model that recapitulates the long-term risk of developing type 2 diabetes following GDM.
妊娠期糖尿病（GDM）是一种常见的产科并发症。有一半的 GDM 患者会发展为 2 型糖尿病。了解其发生机制需要一种没有持续糖尿病的 GDM 动物模型。C57Bl/6J 小鼠对高脂肪、高蔗糖（HFHS）的挑战反应迅速。在这里，我们假设在受孕前的 HFHS 挑战会导致妊娠期间的葡萄糖不耐受。C57Bl/6J 雌性小鼠在交配前 1 或 3 周开始接受 HFHS 喂养，并在整个孕期内持续接受喂养。通过腹腔内葡萄糖耐量试验、胰岛素测量和胰腺胰岛的组织学分析来评估急性 HFHS 的影响。从怀孕前 1 周开始接受 HFHS 喂养的 C57Bl/6J 雌性小鼠出现严重的葡萄糖不耐受，其对葡萄糖的胰岛素反应降低，并且在怀孕期间胰腺胰岛的扩张减少，与对照小鼠相比。当 HFHS 饮食在交配前 3 周开始时，这些 GDM 特征不会发生，这表明急性代谢应激的重要性。此外，HFHS 喂养在未怀孕的雌性小鼠中仅导致轻度胰岛素抵抗。当分娩时停止饮食时，症状在 3 周内得到缓解。然而，在怀孕期间经历葡萄糖不耐受的小鼠在以后的生活中对 HFHS 挑战的反应变得更容易出现葡萄糖不耐受，而不是经历正常妊娠的同基因雌性小鼠，或者在怀孕期间以外的时间接受相同饮食的小鼠。因此，C57Bl/6 小鼠中的急性 HFHS 挑战导致了一种新的、非肥胖的动物模型，该模型重现了 GDM 后发展为 2 型糖尿病的长期风险。
