The influence of somatostatin on glucagon and pancreatic polypeptide secretion in the isolated perfused human pancreas

The current study was undertaken to determine whether intraislet somatostatin regulates glucagon or pancreatic polypeptide (PP) secretion in the human pancreas. A high-affinity, high-specificity monoclonal somatostatin antibody (CURE.S6) was used to immunoneutralize somatostatin in the isolated, perfused human pancreas. Single-pass perfusion was performed in pancreata obtained from cadaveric organ donors using a modified Krebs media with either 3.9 or 12.9 m M glucose. Sequential test periods separated by basal periods were performed with infusion of either exogenous somatostatin-14 (SS-14), CURE.S6, or a combined infusion. Infusion of SS-14 did not significantly alter glucagon or PP secretion during low-glucose or high-glucose perfusion. Immunoneutralization of intraislet somatostatin with CURE.S6 resulted in a significant increase of glucagon secretion under low-glucose conditions (ΔX=15±3 p M) (p<0.05), but did not significantly effect glucagon secretion under high-glucose conditions (ΔX=-2±3 p M) (p=NS). PP secretion remained unchanged during CURE.S6 infusion. Combined infusion of SS-14 and CURE.S6 did not significantly alter glucagon or PP secretion. The data suggest that intraislet somatostatin may have an inhibitory role in the regulation of glucagon secretion during low-glucose conditions and that intraislet somatostatin does not regulate PP secretion in the isolated, perfused human pancreas.