Lawson Health Research Institute, St. Joseph's Health Care, 268 Grosvenor Street, London, Ontario N6A 4V2, Canada.
Curr Vasc Pharmacol. 2021;19(2):141-153. doi: 10.2174/1570161118666200320111209.
Normal pregnancy is associated with increased insulin resistance as a metabolic adaptation to the nutritional demands of the placenta and fetus, and this is amplified in obese mothers. Insulin resistance is normally compensated for by an adaptive increase in pancreatic β-cell mass together with enhanced glucose-stimulated insulin release. Placentally-derived hormones and growth factors are central to the altered pancreatic morphology and function. A failure of β-cells to undergo adaptive change after the first trimester has been linked with gestational diabetes. In the pregnant mouse, an increase in β-cell replication contributes to a 2-3-fold increase in mass peaking in late gestation, depending on the proliferation of existing β-cells, the differentiation of resident progenitor β-cells, or islet cell transdifferentiation. Using mouse models and human studies placenta- and islet of Langerhans-derived molecules have been identified that are likely to contribute to the metabolic adaptations to pregnancy and whose physiology is altered in the obese, glucose-intolerant mother. Maternal obesity during pregnancy can create a pro-inflammatory environment that can disrupt the response of the β-cells to the endocrine signals of pregnancy and limit the adaptive changes in β-cell mass and function, resulting in an increased risk of gestational diabetes.
正常妊娠伴随着胰岛素抵抗的增加，这是一种代谢适应胎盘和胎儿营养需求的方式，而肥胖母亲的这种适应更为明显。胰岛素抵抗通常通过胰腺β细胞质量的适应性增加以及增强的葡萄糖刺激胰岛素释放来代偿。胎盘来源的激素和生长因子是改变胰腺形态和功能的核心。β细胞在孕早期后未能进行适应性改变与妊娠期糖尿病有关。在怀孕的小鼠中，β细胞复制的增加导致质量增加 2-3 倍，在妊娠晚期达到峰值，这取决于现有β细胞的增殖、驻留祖代β细胞的分化或胰岛细胞转分化。使用小鼠模型和人类研究已经鉴定出胎盘和胰岛衍生的分子，这些分子可能有助于妊娠的代谢适应，并且其生理学在肥胖、葡萄糖不耐受的母亲中发生改变。妊娠期间的母体肥胖会产生促炎环境，从而破坏β细胞对妊娠内分泌信号的反应，并限制β细胞质量和功能的适应性改变，导致妊娠期糖尿病的风险增加。
