Glucagon Secretion from the Perfused Rat Pancreas STUDIES WITH GLUCOSE AND CATECHOLAMINES

Gordon C. Weir; Stephen D. Knowlton; Donald B. Martin

doi:10.1172/JCI107887

Glucagon Secretion from the Perfused Rat Pancreas STUDIES WITH GLUCOSE AND CATECHOLAMINES

Gordon C. Weir, Stephen D. Knowlton, and Donald B. Martin

Published December 1, 1974 - More info

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Abstract

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 × 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.