PDF(Pubmed)
Abstract：
Reducing ghrelin by ghrelin gene knockout (GKO), ghrelin-cell ablation, or high-fat diet feeding increases islet size and β-cell mass in male mice. Here we determined if reducing ghrelin also enlarges islets in females and if pregnancy-associated changes in islet size are related to reduced ghrelin. Islet size and β-cell mass were larger (P = .057 for β-cell mass) in female GKO mice. Pregnancy was associated with reduced ghrelin and increased liver-expressed antimicrobial peptide-2 (LEAP2; a ghrelin receptor antagonist) in wild-type mice. Ghrelin deletion and pregnancy each increased islet size (by ∼19.9-30.2% and ∼34.9-46.4%, respectively), percentage of large islets (>25 µm2×103, by ∼21.8-42% and ∼21.2-41.2%, respectively), and β-cell mass (by ∼15.7-23.8% and ∼65.2-76.8%, respectively). Neither islet cross-sectional area, β-cell cross-sectional area, nor β-cell mass correlated with plasma ghrelin, although all positively correlated with LEAP2 (P = .081 for islet cross-sectional area). In ad lib-fed mice, there was an effect of pregnancy, but not ghrelin deletion, to change (raise) plasma insulin without impacting blood glucose. Similarly, there was an effect of pregnancy, but not ghrelin deletion, to change (lower) blood glucose area under the curve during a glucose tolerance test. Thus, genetic deletion of ghrelin increases islet size and β-cell cross-sectional area in female mice, similar to males. Yet, despite pregnancy-associated reductions in ghrelin, other factors appear to govern islet enlargement and changes to insulin sensitivity and glucose tolerance in the setting of pregnancy. In the case of islet size and β-cell mass, one of those factors may be the pregnancy-associated increase in LEAP2.
摘要：
通过ghrelin基因敲除（GKO）减少ghrelin，ghrelin细胞消融，或高脂饮食喂养会增加雄性小鼠的胰岛大小和β细胞质量。这里,我们确定减少ghrelin是否也会扩大女性的胰岛，如果妊娠相关的胰岛大小变化与ghrelin减少有关。雌性GKO小鼠的胰岛大小和β细胞质量较大（β细胞质量P=0.057）。在WT小鼠中,妊娠与ghrelin减少和LEAP2[一种ghrelin受体(GHSR)拮抗剂]增加相关。Ghrelin缺失和怀孕各自增加了胰岛大小(约19.9-30.2%和约34.9-46.4%，分别)，大型胰岛的百分比(>25µm2x103，由〜21.8-42%和〜21.2-41.2%，分别)和β细胞质量(由15.7-23.8%和65.2-76.8%，分别)。两个胰岛横截面积，β细胞横截面积，β细胞质量与血浆ghrelin无关，尽管所有与LEAP2呈正相关（胰岛横截面积P=0.081）。在随意喂养的小鼠中，有怀孕的影响，但不是ghrelin删除，改变（提高）血浆胰岛素而不影响血糖。同样，有怀孕的影响，但不是ghrelin删除，在葡萄糖耐量试验期间改变（降低）曲线下的血糖面积。因此，ghrelin的基因缺失增加雌性小鼠的胰岛大小和β细胞横截面积，类似于男性。然而，尽管与妊娠相关的ghrelin减少，在妊娠期间，其他因素似乎控制着胰岛增大以及胰岛素敏感性和糖耐量的变化。在胰岛大小和β细胞质量的情况下，这些因素之一可能是妊娠相关的LEAP2升高.
