Inhibition of glucagon secretion by exogenous glucagon in the isolated, perfused dog pancreas

To determine if glucagon can inhibit its own secretion, exogenous glucagon was perfused in the isolated canine pancreas at concentrations ranging from 90 to 1050 pg/ml during either stimulation or suppression of endogenous glucagon secretion. When endogenous glucagon secretion was completely suppressed by the addition of 200 mg/dl of glucose to the perfusate, the concentration of glucagon in the venous effluent ranged from 80.8 to 89.9% of the level perfused; these deficits of 10-20% were attributed to uptake and/or degradation of exogenous glucagon by the pancreas. By contrast, when endogenous glucagon secretion was stimulated by perfusing with 10 mM arginine or by glucopenia of 25 mg/dl, there was a significant increase in the glucagon deficit (the efflux glucagon level during glucagon perfusion minus the sum of the pre-perfusion efflux level of endogenous glucagon and the concentration of glucagon perfused); only 60-76% of the expected glucagon concentration was present in the venous efflux. This increase in deficit is assumed to reflect suppression of endogenous glucagon. The glucagon deficit rose progressively with the perfused concentration of glucagon until the deficit reached the approximate level of endogenous glucagon, at which no further increase occurred, suggesting that suppression at that point was complete. To determine if the glucagon-suppressing action of glucagon was mediated by an increase in glucagon-stimulated insulin or somatostatin secretion, these hormones were measured in the various experiments. Insulin and somatostatin increased significantly when glucagon was perfused with the glucose arginine-containing solution but did not rise significantly when the glucopenic buffer was used, although suppression of endogenous glucagon was similar in each instance. It is concluded that glucagon suppresses glucagon secretion. Evidence that insulin and/or somatostatin mediate this action could not be obtained.