Glucose-induced insulin secretion is diminished during the fetal and neonatal period. To investigate whether the “defect” in B-cell secretion is specific for glucose and linked to glucose metabolism, the insulin-releasing effect of three nutrient secretagogues, glucose, glyceraldehyde, and leucine, were compared at different ages of the rat in vivo (1- and 7-day neo-nates) and in vitro (1- and 7-day neonates and adult animals). Intraperitoneal injections produced a marked insulin response to glucose, glyceraldehyde, and leucine in 7-day animals but only small increments that were not significant in 1-day neonates.

The accumulation of insulin from isolated islets of 1-day neonates during 60-min incubations was slightly but significantly enhanced by 11.1-34.4 m M glucose or 40 mM leucine. No response was seen with 1-16 mM glyceraldehyde. By contrast, all three secretagogues markedly stimulated insulin secretion from 7-day and adult islets. However, quantitative relationships differed. Thus, the response from 7-day islets to the highest concentration of glucose was 20%, to glyceraldehyde 10%, and to leucine 50% of adult values. A “basal” concentration of glucose (4.4 mM) amplified glyceraldehyde- or leucine-induced insulin release, but did not influence the age-related differences in secretory response.

The nutrient secregogues induced a small percent stimulation of (32P)-orthophosphate efflux from prelabeled islets of 1-day neonates. This stimulation increased progressively with age. However, in 1- and 7-day islets glucose and leucine stimulated the efflux of 32P more than glyceraldehyde; in adult islets the nutrients were equipotent. Glucose, glyceraldehyde, and leucine increased the accumulation of (3H) cyclic AMP in prelabeled adult but not in 7- or 1-day islets.

The foregoing indicates that the obtunded insulin secretion at birth in the rat may apply to all nutrient secretagogues. Because of the difference in metabolic disposition of tested secretagogues, the secretory limitation cannot be ascribed to faulty glycolysis but must involve some communally shared, probably early, step in stimulus-secretion coupling. Continued maturation includes preferential development of the secretory responsiveness to some secretagogues.

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