Adaptive changes in insulin secretion by islets from neonatal rats raised on a high-carbohydrate formula

Artificial rearing of neonatal rats on a high-carbohydrate (HC) milk formul a resulted in the immediate onset of hyperinsulinemia. This study examines, in islets of 12-day-old HC rats, adaptive changes that support the hyperin sulinemic state. Increases in plasma glucagon-like peptide-1 (GLP-1) levels and islet GLP-1 receptor mRNA supported increased insulin secretion by HC islets. Isolated HC islets, but not mother-fed (MF) islets, secreted modera te amounts of insulin in a glucose-and Ca2+-independent manner. Under strin gent Ca2+-free conditions and in the presence of glucose, GLP-1 plus acetyl choline augmented insulin release to a larger extent in HC islets. Levels o f adenylyl cyclase type VI mRNA and activities of protein kinase A, protein kinase C, and calcium calmodulin kinase II were increased in HC islets. A tenfold increase in norepinephrine concentration was required to inhibit in sulin secretion in HC islets compared with MF islets, indicating reduced se nsitivity to adrenergic signals. This study shows that significant alterati ons at proximal and distal sites of the insulin secretory pathway in HC isl ets may support the hyperinsulinemic state of these rats.