Regulation of pancreatic polypeptide secretion in the isolated perfused human pancreas

The isolated perfused human pancreas was used as a model to assess factors mediating the pancreatic polypeptide cell response to glucose, insulin, gastric inhibitory polypeptide, and splanchnic nerve stimulation. Pancreases obtained from 18 cadaveric organ donors were isolated and perfused by way of the splenic artery utilizing a Krebs bicarbonate buffer in a single-pass perfusion system. Hormonal stimulation and inhibition of pancreatic polypeptide secretion were assessed, as was the influence of direct electrical stimulation of celiac neural fibers innervating the pancreas. In this in vitro human model, pancreatic polypeptide cell secretion was inhibited by hyperglycemia, although the presence of gastric inhibitory polypeptide augmented the pancreatic polypeptide cell response. Perfusion with low levels of insulin and splanchnic nerve stimulation augmented the response of the pancreatic polypeptide cell to hyperglycemia and gastric inhibitory polypeptide. Since the immunoreactive pancreatic polypeptide response was augmented when insulin and somatostatin release was inhibited by perfusion insulin or nerve stimulation, we conclude that the pancreatic polypeptide cell is regulated by the ambient degree of somatostatin release, insulin release, or both. These findings support a centrifugal pattern of intraislet blood flow.