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 somat ostatin regulates glucagon or pancreatic polypeptide (PP) secretion in the human pancreas. A high-affinity, high-specificity monoclonal soma tostatin antibody (CURE.S6) was used to immunoneutralize somatostatin in the isolated, perfused human pancreas. Single-pass perfusion was pe rformed in pancreata obtained from cadaveric organ donors using a modi fied Krebs media with either 3.9 or 12.9 mM glucose. Sequential test p eriods separated by basal periods were performed with infusion of eith er exogenous somatostatin-14 (SS-14), CURE.S6, or a combined infusion. Infusion of SS- 14 did not significantly alter glucagon or PP secreti on during low-glucose or high-glucose perfusion. Immunoneutralization of intraislet somatostatin with CURE.S6 resulted in a significant incr ease of glucagon secretion under low-glucose conditions (Delta X = 15 +/- 3 pM) (p < 0.05), but did not significantly effect glucagon secret ion under high-glucose conditions (Delta T = -2 +/- 3 pM) (p = NS). PP secretion remained unchanged during CURE.S6 infusion. Combined infusi on of SS-14 and CURE.S6 did not significantly alter glucagon or PP sec retion. The data suggest that intraislet somatostatin may have an inhi bitory role in the regulation of glucagon secretion during low-glucose conditions and that intraislet somatostatin does not regulate PP secr etion in the isolated, perfused human pancreas.