Petrik J, Srinivasan M, Aalinkeel R, Coukell S, Arany E, Patel M S, Hill D J
Lawson Research Institute, St. Joseph's Health Centre, London, Ontario N6A 4V2, Canada.
Pediatr Res. 2001 Jan;49(1):84-92. doi: 10.1203/00006450-200101000-00019.
Neonatal rats fed a high-carbohydrate (HC) formula by gastrostomy are hyperinsulinemic but normoglycemic. We determined whether HC formula altered pancreatic islet cell ontogeny. Rats were reared from d 4 on an HC formula or a high-fat formula, or were allowed to suckle naturally, and the pancreata were examined histologically from animals < or =24 d of age. The mean area of individual islets was reduced, but islet number was increased in HC rats compared with mother-fed or high fat-fed animals, which were similar. Islets from HC animals were relatively deficient in alpha cells and had a greater incidence of islet cells with fragmented DNA, indicative of apoptosis. Ductal epithelium, a source of new islets by neogenesis, had a greater incidence of cells staining immunopositive for proliferating cell nuclear antigen, a marker of cell replication, and a lower incidence of apoptosis. The islet cell mitogen and survival factor, IGF-II, had a reduced mRNA expression in whole pancreas from HC animals. The relative area of islet cells demonstrating IGF-II immunoreactivity was reduced in HC-fed rats versus controls, although a greater percentage of ductal epithelial cells were immunopositive. HC formula alters islet cell ontogeny by affecting islet size and number, which may be linked to an altered IGF-II expression.
通过胃造口术喂食高碳水化合物(HC)配方奶的新生大鼠存在高胰岛素血症但血糖正常。我们确定了HC配方奶是否改变了胰岛细胞的个体发生。大鼠从第4天起分别用HC配方奶、高脂肪配方奶饲养,或自然哺乳,对年龄小于或等于24天的动物的胰腺进行组织学检查。与由母鼠喂养或高脂肪喂养的动物(二者情况相似)相比,HC大鼠单个胰岛的平均面积减小,但胰岛数量增加。HC动物的胰岛α细胞相对缺乏,且胰岛细胞中DNA片段化(表明细胞凋亡)的发生率更高。导管上皮是通过新生形成新胰岛的来源,其细胞中增殖细胞核抗原(一种细胞复制标志物)免疫阳性染色的发生率更高,而细胞凋亡的发生率更低。胰岛细胞有丝分裂原和存活因子IGF-II在HC动物全胰腺中的mRNA表达降低。与对照组相比,HC喂养大鼠中显示IGF-II免疫反应性的胰岛细胞相对面积减小,尽管导管上皮细胞免疫阳性的百分比更高。HC配方奶通过影响胰岛大小和数量改变胰岛细胞个体发生,这可能与IGF-II表达改变有关。