A dietary intervention (high carbohydrate) during the neonatal period causes islet dysfunction in rats

Artificial rearing of 4-day-old rat pups on a high-carbohydrate (HC) milk f ormula results in the immediate onset of hyperinsulinemia. To evaluate thes e early changes, studies on pancreatic function were carried out on 12-day- old HC rats and compared with age-matched mother-fed (MF) pups. The plasma insulin and glucagon contents were increased sixfold and twofold, respectiv ely, in HC rats compared with MF rats. There was a distinct leftward shift in the glucose-stimulated insulin secretory pattern for HC islets. HC islet s secreted insulin in the absence of any added glucose and in the presence of Ca2+ channel inhibitors. The activities of glucokinase, hexokinase, glyc eraldehyde-3-phosphate dehydrogenase, and pyruvate dehydrogenase complex we re significantly increased in HC islets compared with MF islets. The protei n contents of GLUT-2 and hexokinase were significantly increased in HC isle ts. These findings indicate that a nutritional intervention in the form of a HC formula only during the suckling period has a profound influence on pa ncreatic function, causing the onset of hyperinsulinemia.