NEONATAL RAT DIETARY CARBOHYDRATE AFFECTS PANCREATIC-ISLET INSULIN-SECRETION IN ADULTS AND PROGENY

Neonatal rat pups were artificially reared on isocaloric diets high in carbohydrate (HC) or high in fat (HF) or were naturally reared on mot her's milk (MF). The HC adult rats were hyperinsulinemic, normoglycemi c, and obese. This study investigates pancreatic islet insulin release (IR) of the adult first-generation (1-) diet-regulated animals and th eir second-generation (2-) progeny. Male rat 1-HC islets had higher ba sal IR than either 1-MF or 1-HF control groups. In addition, glucose ( 17 mM) failed to increase IR above basal values in 1-HC islets, wherea s it stimulated IR in 1-MF and 1-HF islets. Similar secretory response s were evoked by 2-ketoisocaproic acid (2-KIC). Female rat 1-MF and 1- HF islets also had higher glucose-stimulated IR compared with 1-HC isl ets. Male rat 2-HC islets had higher basal IR and reduced sensitivity to glucose and 2-KIC compared with 2-MF islets, which coincided with h yperinsulinemia. Glyceraldehyde-3-phosphate dehydrogenase activity in I-HC and 2-HC islets was higher than in MF islets. These data suggest that basal IR is higher in islets isolated from animals reared as neon ates on a diet high in carbohydrate. Alterations in beta-cell metaboli sm and secretion probably contribute to the hyperinsulinemia, reduced glucose sensitivity, and glucose intolerance characteristic of this ra t model.