This communication reports studies dealing with the action of glucagon, theophylline, cyclic adenosine monophosphate (3′5′.AMP) and phenoxybenzamine on insulin secretion, and their possible interaction with glucose and diazoxide.

Diazoxide inhibited both phases of insulin secretion produced by glucose. This blocking action was suppressed when the alpha-blocking phenoxybenzamine was present.

Glucagon produced a uniform pattern of insulin secretion when perfused alone. A one-minute pulse of 3′5′.AMP produced a sharp peak of insulin secretion. Neither glucagon nor 3′5′.AMP effects were inhibited by diazoxide.

Theophylline did not increase the basal insulin-secretion. However, when perfused together with glucose, theophylline stimulated additional insulin secretion, significantly higher than that produced by glucose alone.

When combinations of glucagon plus glucose, 3′5′.AMP plus glucose and theophylline plus glucose, were perfused, diazoxide blocked the secretion of insulin stimulated by glucose, but not that produced by glucagon, 3′5′.AMP or theophylline. This suggests that glucagon, 3′5′.AMP and theophylline stimulate insulin secretion by actingon mechanismsdifferent from the ones stimulated by glucose

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