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

J Clin Invest. 1974 Dec;54(6):1403-12. doi: 10.1172/JCI107887.


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.

MeSH terms

  • Animals
  • Cyclic AMP / physiology
  • Deoxyglucose / physiology
  • Depression, Chemical
  • Drug Synergism
  • Epinephrine / pharmacology*
  • Glucagon / metabolism*
  • Glucose / analysis
  • Glucose / pharmacology*
  • Glucose / physiology
  • Insulin / metabolism
  • Insulin Secretion
  • Male
  • Norepinephrine / pharmacology*
  • Pancreas / drug effects*
  • Pancreas / metabolism
  • Perfusion
  • Radioimmunoassay
  • Rats
  • Theophylline / pharmacology


  • Insulin
  • Glucagon
  • Deoxyglucose
  • Theophylline
  • Cyclic AMP
  • Glucose
  • Norepinephrine
  • Epinephrine