Glucagon secretion from the perfused rat pancreas. Studies with glucose and catecholamines

The isolated in situ perfused rat pancreas was used to study glucose and catecholamine control of glucagon secretion, and to investigate the possible role of endogenous cyclic AMP as a mediator of this secretory process. When perfusate glucose was acutely dropped from 100 to 25 mg/100 ml, glucagon was released in a biphasic pattern with an early spike and a later plateau-like response. 300 mg/100 ml glucose suppressed glucagon secretion to near the detection limit of the radioimmunoassay (15 pg/ml). When perfusate glucose was dropped from 300 to 25 mg/100 ml, a delayed, relatively small peak occurred suggesting persisting alpha cell suppression by prior high glucose exposure. 2-Deoxy d-glucose stimulated glucagon secretion and inhibited insulin secretion. Glucagon was secreted in a biphasic pattern in response to both 2.7 x 10(-7) M epinephrine and norepinephrine. The glucagon response to epinephrine was markedly suppressed by glucose at 300 mg/100 ml, and the biphasic response pattern was obliterated. Glucose evoked a two-phase insulin secretory pattern, and the second phase was markedly and rapidly inhibited by epinephrine. Pancreases were perfused with glucose at 300 mg/100 ml which was then lowered to 80 mg/100 ml. 5 min later, epinephrine was infused and definite blunting of the first-phase spike occurred. 10 mM theophylline produced modest rapid uniphasic stimulation of glucagon release, and, in addition, caused enhancement of epinephrine-stimulated glucagon release. An inhibitory influence upon epinephrine-stimulated glucagon was observed as well. Insulin secretion was stimulated by 10 mM theophylline, and this stimulation was inhibited by epinephrine.