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

Neonatal rats fed a high-carbohydrate (HC) formula by gastrostomy are hyper insulinemic but normoglycemic. We determined whether HC formula altered pan creatic 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 less than or equal to 24 d of age . The mean area of individual islets was reduced, but islet number was incr eased in HC rats compared with mother-fed or high fat-fed animals, which we re similar. Islets from HC animals were relatively deficient in cu cells an d 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 n uclear antigen, a marker of cell replication, and a lower incidence of apop tosis. The islet cell mitogen and survival factor, IGF-II, had a reduced mR NA expression in whole pancreas from HC animals. The relative area of islet cells demonstrating IGF-II immunoreactivity was reduced in HC-fed rats ver sus controls, although a greater percentage of ductal epithelial cells were immunopositive. HC formula alters islet cell ontogeny by affecting islet s ize and number, which may be linked to an altered IGF-II expression.