A long-term high-carbohydrate diet causes an altered ontogeny of pancreatic islets of Langerhans in the neonatal rat.

Abstract

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.