The adenyl cyclase-cyclic AMP system, aside from being a mediator of the actions of several hormones, is believed to play an important role in the secretory mechanism of some of these hormones. In young, healthy, nonobese volunteers, we have studied the effect of a large dose (1 gm.) of a cAMP phosphodiesterase inhibitor (aminophylline) on basal plasma glucagon and insulin levels and on the responses of these two hormones to two different doses of arginine.
With a high (468 mg./kg.) and a low (156 mg./kg.) dose of arginine, similar maximal peaks of glucagon concentration were reached, indicating that the level of aminoacidemia reached with the low dose was sufficient to elicit an almost maximal acute response. Plasma insulin and glucose increased as expected after the arginine doses.
With aminophylline alone, plasma insulin and glucose increased slightly but consistently while the level of circulating glucagon did not change (range of the means, 111 pg./ml. ± 28 to 133 pg./ml. ± 25). Aminophylline pretreatment significantly lowered the glucagon response in the late part of the curve corresponding to the high dose of arginine. This inhibitory effect of the xanthine derivative could be due to: (1) peripheral effects of aminophylline, such as increased mobilization of FFA; (2) enhanced removal of glucagon from plasma; (3) direct suppressor effect of cAMP on the alpha cell secretory mechanism. At any rate, this effect of aminophylline seems to be either a retarded one or only present in the late phase of glucagon secretion.