Maternal pancreatic beta-cell mass (BCM) increases during pregnancy to compensate for relative insulin resistance. If BCM expansion is suboptimal, gestational diabetes mellitus can develop. Alpha-cell mass (ACM) also changes during pregnancy, but there is a lack of information about α-cell plasticity in pregnancy and whether α- to β-cell transdifferentiation can occur. To investigate this, we used a mouse model of gestational glucose intolerance induced by feeding low-protein (LP) diet from conception until weaning and compared pregnant female offspring to control diet-fed animals. Control and LP pancreata were collected for immunohistochemical analysis and serum glucagon levels were measured. In order to lineage trace α- to β-cell conversion, we utilized transgenic mice expressing yellow fluorescent protein behind the proglucagon gene promoter (Gcg-Cre/YFP) and collected pancreata for histology at various gestational timepoints. Alpha-cell proliferation increased significantly at gestational day (GD) 9.5 in control pregnancies resulting in an increased ACM at GD18.5, and this was significantly reduced in LP animals. Despite these changes, serum glucagon was higher in LP mice at GD18.5. Pregnant Gcg-Cre/YFP mice showed no increase in the abundance of insulin⁺YFP⁺glucagon^– cells (phenotypic β-cells). A second population of insulin⁺YFP⁺glucagon⁺ cells was identified which also did not alter during pregnancy. However, there was an altered anatomical distribution within islets with fewer insulin⁺YFP⁺glucagon^– cells but more insulin⁺YFP⁺glucagon⁺ cells being present in the islet mantle at GD18.5. These findings demonstrate that dynamic changes in ACM occur during normal pregnancy and were altered in glucose-intolerant pregnancies.

孕期母体胰腺 β 细胞质量 (BCM) 增加以补偿相对的胰岛素抵抗。如果 BCM 扩张不理想，可能会发展为妊娠糖尿病。妊娠期间 α 细胞质量 (ACM) 也会发生变化，但缺乏关于妊娠期间 α 细胞可塑性以及是否会发生 α 至 β 细胞转分化的信息。为了研究这一点，我们使用了从受孕到断奶期间喂食低蛋白 (LP) 饮食诱导的妊娠期葡萄糖不耐受的小鼠模型，并将怀孕的雌性后代与对照饮食喂养的动物进行比较。收集对照和 LP 胰腺进行免疫组织化学分析并测量血清胰高血糖素水平。为了谱系追踪 α 到 β 细胞的转化，我们利用在胰高血糖素前体基因启动子 (Gcg-Cre/YFP) 后面表达黄色荧光蛋白的转基因小鼠，并在不同的妊娠时间点收集胰腺进行组织学检查。在对照组妊娠中，α 细胞增殖在妊娠天 (GD) 9.5 显着增加，导致 ACM 在 GD18.5 增加，而这在 LP 动物中显着降低。尽管有这些变化，LP 小鼠的血清胰高血糖素在 GD18.5 时更高。怀孕的 Gcg-Cre/YFP 小鼠的胰岛素丰度没有增加 在 GD18.5 时，LP 小鼠的血清胰高血糖素较高。怀孕的 Gcg-Cre/YFP 小鼠的胰岛素丰度没有增加 在 GD18.5 时，LP 小鼠的血清胰高血糖素较高。怀孕的 Gcg-Cre/YFP 小鼠的胰岛素丰度没有增加⁺ YFP ⁺胰高血糖素^–细胞（表型 β 细胞）。确定了第二个胰岛素⁺ YFP ⁺胰高血糖素⁺细胞群，在怀孕期间也没有改变。^{然而，胰岛内的解剖分布发生了变化，胰岛素+} YFP ⁺胰高血糖素^-细胞较少，但在 GD18.5 时胰岛地幔中存在更多的胰岛素⁺ YFP ⁺胰高血糖素^+细胞。这些发现表明，ACM 的动态变化发生在正常妊娠期间，并在葡萄糖不耐受妊娠中发生改变。