Gestational diabetes adversely affects pancreatic islet development and function in the rat offspring

Gestational diabetes mellitus (GDM) exposure and obesity are strong risk factors for type 2 diabetes development; however, the connections between GDM exposure, postnatal diet and islet dysfunction in offspring metabolic health remain unclear. Reduced glucose-stimulated insulin secretion was observed in islets isolated from 15-week-old offspring prenatally exposed to GDM, which was exacerbated by postnatal HFS consumption. In the HFS-fed offspring of Lean dams, islet size and number increased, an adaptation that was not observed in the HFS-fed offspring of GDM dams. Islets from GDM exposed offspring revealed upregulation of 102 genes (e.g. Sod2, Il1b) and 13 downregulated genes. In the GDM offspring that consumed a postnatal HFS-diet, 126 genes were significantly upregulated (e.g. Ccl2, Rps14, Atp5f1) and 17 genes were downregulated (e.g. Hnf1a, Slc2a2). These results demonstrate that GDM exposure induced changes in gene expression in the young adult rat offspring that worsen islet function and whole-body glucose homeostasis.妊娠期糖尿病（Gestational diabetes mellitus, GDM）暴露与肥胖均为2型糖尿病发生的强风险因子；然而，GDM暴露、产后饮食与子代代谢健康中胰岛功能异常三者之间的关联仍不明确。研究发现，产前暴露于GDM的15周龄子代大鼠的分离胰岛中，葡萄糖刺激胰岛素分泌功能受损，且该缺陷会因产后摄入HFS饲料而进一步加剧。在喂食HFS饲料的瘦型母鼠子代中，胰岛体积与数量均有所增加，这种适应性变化在喂食HFS饲料的GDM母鼠子代中并未观察到。对暴露于GDM的子代大鼠胰岛进行检测可见，102个基因（如Sod2、Il1b）表达上调，另有13个基因表达下调。而在产后食用HFS饲料的GDM暴露子代大鼠中，共有126个基因显著上调（如Ccl2、Rps14、Atp5f1），17个基因显著下调（如Hnf1a、Slc2a2）。上述结果表明，产前GDM暴露会改变年轻成年子代大鼠的基因表达，进而加剧胰岛功能异常与全身葡萄糖稳态失衡。