Insulin secretory dynamics during development of rat pancreas

Abstract

The dynamics of insulin secretion during development of the fetal rat pancreas were investigated. The time of onset of glucose-induced insulin secretion was of special interest. Pancreases from 15-22 day old fetal rats were perifused in vitro with low (0.5 or 0.9 mg/ml) or high (5 mg/ml) concentrations of glucose in the presence or absence of arginine and leucine. Insulin levels in the perifusate were determined by radioimmunoassay. At day 17, a significant increase in perifusate insulin level was observed in response to arginine and leucine (each at 5 mM). This response was independent of a high concentration of glucose. Perifusate insulin levels were augmented when the concentration of amino acids was kept constant and the glucose concentration was changed from a high level to a low level. On day 20, a monophasic, rapid-onset short-duration rise in insulin release with a high glucose concentration was observed. This response was enhanced by acetylcholine (2.7 .times. 10-9 M). At days 21 and 22, insulin levels rose rapidly in the presence of high glucose and remained elevated. There is considerable precision in the timing of the onset and maturation of the glucose-induced insulin secretory response prenatally, and insulin secretion by the fetal .beta.-cell varies with the stimulus applied.