White Alicia, Louey Samantha, Chang Eileen I, Boehmer Brit H, Goldstrohm David, Jonker Sonnet S, Rozance Paul J
Department of Pediatrics, Perinatal Research Center, University of Colorado Denver School of Medicine, Aurora, Colorado.
Center for Developmental Health, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon.
Physiol Rep. 2018 Sep;6(17):e13840. doi: 10.14814/phy2.13840.
Fetal insulin is critical for regulation of growth. Insulin concentrations are partly determined by the amount of β-cells present and their insulin content. Insulin-like growth factor-1 (IGF-1) is a fetal anabolic growth factor which also impacts β-cell mass in models of β-cell injury and diabetes. The extent to which circulating concentrations of IGF-1 impact fetal β-cell mass and pancreatic insulin content is unknown. We hypothesized that an infusion of an IGF-1 analog for 1 week into the late gestation fetal sheep circulation would increase β-cell mass, pancreatic islet size, and pancreatic insulin content. After the 1-week infusion, pancreatic insulin concentrations were 80% higher than control fetuses (P < 0.05), but there were no differences in β-cell area, β-cell mass, or pancreatic vascularity. However, pancreatic islet vascularity was 15% higher in IGF-1 fetuses and pancreatic VEGFA, HGF, IGF1, and IGF2 mRNA expressions were 70-90% higher in IGF-1 fetuses compared to control fetuses (P < 0.05). Plasma oxygen, glucose, and insulin concentrations were 25%, 22%, and 84% lower in IGF-1 fetuses, respectively (P < 0.05). The previously described role for IGF-1 as a β-cell growth factor may be more relevant for local paracrine signaling in the pancreas compared to circulating endocrine signaling.
胎儿胰岛素对生长调节至关重要。胰岛素浓度部分取决于β细胞的数量及其胰岛素含量。胰岛素样生长因子-1（IGF-1）是一种胎儿合成代谢生长因子，在β细胞损伤和糖尿病模型中也会影响β细胞量。循环中的IGF-1浓度对胎儿β细胞量和胰腺胰岛素含量的影响程度尚不清楚。我们假设，在妊娠晚期胎儿绵羊循环中输注IGF-1类似物1周会增加β细胞量、胰岛大小和胰腺胰岛素含量。输注1周后，胰腺胰岛素浓度比对照胎儿高80%（P<0.05），但β细胞面积、β细胞量或胰腺血管并无差异。然而，IGF-1处理的胎儿胰腺胰岛血管增加了15%，与对照胎儿相比，IGF-1处理的胎儿胰腺VEGFA、HGF、IGF1和IGF2 mRNA表达高70%-90%（P<0.05）。IGF-1处理的胎儿血浆氧、葡萄糖和胰岛素浓度分别降低了25%、22%和84%（P<0.05）。与循环内分泌信号相比，先前描述的IGF-1作为β细胞生长因子的作用可能与胰腺中的局部旁分泌信号更相关。
