Dynamics of Insulin Release from the Foetal and Neonatal Rat Pancreas

Abstract. The dynamics of glucose-stimulated insulin release from pieces of foetal and neonatal rat pancreas were studied in an in vitro perifusion system. During an initial 60-min. equilibration period, the tissue was perifused with a phosphate-buffered medium containing 0.4 mg/ml glucose. This was followed by a 40-min. stimulation period, in which the medium glucose concentration was 3.0 mg/ml. Tissue obtained from foetuses of 21.5 days' gestation displayed only a small initial peak of insulin release when exposed to a high glucose concentration. At one day post partum, a low initial response to glucose was followed by a small but significant secondary rise in insulin secretion. At six days of age, a pronounced immediate response and a subsequent constant high level of insulin output were recorded during the stimulation period. At one day of age, the addition of 5 mM arginine to the perifusion medium during the stimulation period caused a marked increase of insulin output during both the early and the late phase, compared with glucose alone. – The present data indicate that the mechanism responsible for the initial phase of glucose-stimulated insulin release is already present in the rat during late foetal life, although it is probably not completely mature. The development of the second phase of the secretory response seems to be an essentially postnatal event. The dynamics of insulin release in the immature rat appear to be similar to those reported in prediabetic and some diabetic individuals. The intriguing possibility that the predisposition to diabetes may be associated with a lack of normal development of the insulin secreting mechanism seems to deserve further consideration.