背景:怀孕期间胰岛β细胞团扩张,但是潜在的机制还没有完全理解。这项研究检查了怀孕和自助餐厅饮食对胰岛形态的影响,相关的细胞增殖/凋亡率以及β细胞谱系。
方法:非妊娠和妊娠Ins1Cre/+;Rosa26-eYFP转基因小鼠维持正常或高脂肪自助餐,妊娠18天获得的胰腺组织。胰岛形态的免疫组织化学改变,β-/α-细胞增殖和凋亡,以及胰岛细胞身份,评估新生和导管细胞转分化。
结果:妊娠正常饮食小鼠显示体重和血糖增加。自助餐厅喂养减轻了这种体重增加,同时引起明显的高血糖。维持正常饮食的妊娠小鼠表现出胰岛和β细胞区域的典型扩张,由于增加的β细胞增殖和存活以及导管向β细胞转分化和β细胞新生,伴随着减少的β细胞去分化。这种妊娠诱导的胰岛适应受到自助餐厅饮食的严重限制。因此,这些小鼠的胰岛表现出高水平的β细胞凋亡和去分化,伴随着β细胞增殖的减少和缺乏妊娠诱导的β细胞新生和转分化,在正常饮食的怀孕小鼠中观察到完全相反的胰岛细胞修饰。
结论:妊娠期间β细胞群的增加是通过各种机制产生的,包括现有β细胞的增殖和存活,导管细胞的转分化以及β细胞新生。值得注意的是,自助餐厅喂养几乎完全取消了妊娠诱导的胰岛适应,这可能有助于在饮食引起的代谢应激的情况下妊娠糖尿病的发展。
BACKGROUND: Pancreatic islet β-cell mass expands during pregnancy, but underlying mechanisms are not fully understood. This study examines the impact of pregnancy and cafeteria diet on islet morphology, associated cellular proliferation/apoptosis rates as well as β-cell lineage.
METHODS: Non-pregnant and pregnant Ins1Cre/+;Rosa26-eYFP transgenic mice were maintained on either normal or high-fat cafeteria diet, with pancreatic tissue obtained at 18 days gestation. Immunohistochemical changes in islet morphology, β-/α-cell proliferation and apoptosis, as well as islet cell identity, neogenesis and ductal cell
transdifferentiation were assessed.
RESULTS: Pregnant normal diet mice displayed an increase in body weight and glycaemia. Cafeteria feeding attenuated this weight gain while causing overt hyperglycaemia. Pregnant mice maintained on a normal diet exhibited typical expansion in islet and β-cell area, owing to increased β-cell proliferation and survival as well as ductal to β-cell
transdifferentiation and β-cell neogenesis, alongside decreased β-cell dedifferentiation. Such pregnancy-induced islet adaptations were severely restricted by cafeteria diet. Accordingly, islets from these mice displayed high levels of β-cell apoptosis and dedifferentiation, together with diminished β-cell proliferation and lack of pregnancy-induced β-cell neogenesis and
transdifferentiation, entirely opposing islet cell modifications observed in pregnant mice maintained on a normal diet.
CONCLUSIONS: Augmentation of β-cell mass during gestation arises through various mechanisms that include proliferation and survival of existing β-cells,
transdifferentiation of ductal cells as well as β-cell neogenesis. Remarkably, cafeteria feeding almost entirely annuls pregnancy-induced islet adaptations, which may contribute to the development of gestational diabetes in the setting of dietary provoked metabolic stress.