A CRITICAL PERIOD IN THE DEVELOPMENT OF THE INSULIN SECRETORY RESPONSE TO GLUCOSE IN FETAL-RAT PANCREAS

Insulin secretion by fetal rat pancreas was studied at 19.5 and 20.5 days of gestation. Over this 24-hour period, the response to glucose changed rapidly from one that is insensitive to the calcium channel antagonist nitrendipine but markedly enhanced by the presence of the inhibitor of fatty acid oxidation 2-bromostearate, to one that is larger, sensitive to nitrendipine but now not enhanced by 2-bromostearate. The 19.5-day pancreas that is not affected by nitrendipine when responding to glucose alone, is inhibited by nitrendipine when the response to glucose is enhanced by 2-bromostearate. The data suggest a possible metabolic change in the developing B-cell in which fatty acid oxidation is decreased, glucose oxidation increased, and a change in stimulus-secretion coupling from a (KATP) channel-independent mechanism alone, to a combination of that system with the (KATP) channel-dependent system. This could be achieved by a simple increase in the strength of the signal from glucose metabolism.