Pancreatic immunoreactive somatostatin release.

Abstract

The location of the somatostatin-containing D-cells of the pancreatic islets between the .alpha.- and .beta.-cells suggests that their function might be to inhibit insulin and/or glucagon secretion by these neighboring cells. To determine if insulin and/or glucagon, in concentrations that might be present in the extracellular space surrounding the D-cells, stimulate immunoreactive somatostatin (IRS) release, 10 .mu.g of glucagon or 10 milliunits of insulin/ml was perfused in 11 isolated dog pancreases, for 40 min in 7 experiments and for 100 min in 4 experiments. In 8 of the 9 experiments in which glucagon was perfused, a prompt and significant rise in mean IRS release, ranging from 71-128% above the control level, was observed. In the 8 experiments in which insulin was perfused, IRS did not increase during the first 40 min; in the two 100 min insulin experiments, it rose during the final 50 min. To determine the effect of an .alpha.- and .beta.-cell secretogogue on IRS release, 20 mM arginine was perfused for 60 min in 6 experiments. In all, IRS rose within 3 min and reached a level 71-465% above the control, remaining significantly elevated throughout the perfusion, while glucagon and insulin rose to peak levels at 2 min and then declined somewhat despite continuing arginine perfusion. Perfusion of the normal dog pancrease with high doses of glucagon or arginine is was indicated. Apparently accompanied by a prompt increase in IRS release; a local feedback circuit involving A- and D-cells was indicated. Insulin appears not to augment IRS release, at least not promptly, but IRS stimulated by local endogenous glucagon could inhibit the .beta.-cell response to locally secreted glucagon and thereby influence the composition of the insulin/glucagon secretion mixture.