SPLANCHNIC NEURAL REGULATION OF SOMATOSTATIN SECRETION IN THE ISOLATED-PERFUSED HUMAN PANCREAS

Objective The somatostatin-secreting delta cells in the islets of Lang erhans appear to be regulated by neural mechanisms that have not been defined clearly. In this study, the celiac neural bundle of the human pancreas was electrically stimulated in the presence and absence of se lective neural antagonists. Summary Background Data The authors previo usly reported on studies of the splanchnic neural regulation of insuli n, glucagon, and pancreatic polypeptide secretion. In these studies, a lpha-adrenergic fibers appeared to have a predominant effect, strongly inhibiting the secretion of insulin, glucagon, and pancreatic polypep tide secretion. Cholinergic fibers appeared to stimulate strongly, alt hough beta-adrenergic fibers weakly stimulated, the secretion of these hormones. Investigations of neural regulatory mechanisms governing hu man somatostatin release in vitro have not been previously reported. M ethods Pancreata were obtained from eight cadaveric organ donors. The isolated perfused human pancreas technique was used to assess the regu lation of somatostatin secretion by the various neural fibers containe d within the celiac plexus. The secretory response of somatostatin was examined in the presence of 16.7 mmol/L glucose, with and without neu ral stimulation, and specific neural antagonists. Results The basal so matostatin secretion was 88 +/- 26 fmol/g/min and increased 131 +/- 23 % (n = 8, p < 0.01) in response to 16.7 mmol/L glucose. The augmentati on seen with glucose was inhibited 66 +/- 22% (n = 8, p < 0.05) during celiac neural bundle stimulation. Alpha-adrenergic blockade resulted in a 90 +/- 30% (n = 6, p < 0.01) augmentation of somatostatin release . Beta-adrenergic blockade caused a 13 +/- 2% (n = 6, p < 0.05) suppre ssion of somatostatin release. Complete adrenergic blockade resulted i n a 25 +/- 23% (n = 5, p = not significant) inhibition of somatostalin release. Cholinergic blockade resulted in a 40 +/- 10% (n = 6, p < 0. 02) suppression of somatostatin release. Conclusions The predominant e ffect of celiac neural bundle stimulation was inhibition of somatostat in secretion through an alpha-adrenergic effect. Beta-adrenergic fiber s stimulate somatostatin secretion; cholinergic fibers have a negligib le effect on somatostatin secretion. These data suggest that the splan chnic innervation of the pancreas has a potent regulatory role in soma tostatin release in this in vitro human model.