No abstract

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 insulinreleasing effect of three nutrient secretagogues, glucose, glyceraldehyde, and leucine, were compared at different ages of the rat in vivo (1-and 7-day neonates) 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 riiM 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 ( 32 P)-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 32 P more than glyceraldehyde; in adult islets the nutrients were equipotent. Glucose, glyceraldehyde, and leucine increased the accumulation of ( 3 H) cyclic AMP in preiabeled 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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The role of calcium as an intracellular messenger in the activation of eukaryotic cells is discussed. Particular emphasis is devoted to: (1) the interrelationship between cell activation by chemical stimuli and alterations in intracellular calcium metabolism, and (2) the interrelated roles of calcium and the cyclic nucleotides, cyclic AMP and cyclic GMP, in achieving the final integrated, co-ordinated cellular response.