Evidence for a Feedback Inhibition of Insulin on Insulin Secretion in the Isolated, Perfused Canine Pancreas

Abstract

An isolated in vitro canine pancreas per fusion preparation is described which is suitable for prolonged (five hours) study of insulin secretion. The preparation remains in good condition throughout the experimental period judged by various parameters. Feedback inhibition of insulin on insulin secretion was studied in the preparation. Experiments were performed at different concentrations of glucose in the influx medium. At 150 mg. per cent of glucose a considerable reduction of the insulin secretion was obtained when exogenous porcine insulin was added to the influx medium in concentrations from 180 μU./ml. to 420 μU./ml. In eight experiments where the exogenous insulin concentration in the influx medium was equal to or exceeded pre-inhibition efflux values the obtained insulin inhibition amounted to 25-78 per cent of the pre-inhibition values. In one of the eight experiments the exogenous insulin concentration was less than the pre-inhibition value; however, the same effect was obtained. A feedback mechanism of insulin on insulin secretion from the beta cell has thus been demonstrated at levels of perfusate insulin which occur in vivo.