title: The influence of somatostatin on glucagon and pancreatic polypeptide secretion in the isolated perfused human pancreas.
abstract: 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 mM 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 (delta X = 15 +/- 3 pM) (p < 0.05), but did not significantly effect glucagon secretion under high-glucose conditions (delta X = -2 +/- 3 pM) (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.
authors.affiliation: Department of Surgery, VAMC-West Los Angeles, CA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kleinman
authors.forename: R
authors.initials: R
authors.lastname: Gingerich
authors.forename: G
authors.initials: G
authors.lastname: Ohning
authors.forename: H
authors.initials: H
authors.lastname: Wong
authors.forename: K
authors.initials: K
authors.lastname: Olthoff
authors.forename: J
authors.initials: J
authors.lastname: Walsh
authors.forename: F C
authors.initials: FC
authors.lastname: Brunicardi
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D002648:Child; D005260:Female; D005934:Glucagon / Q000378:metabolism*; D006801:Humans; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010191:Pancreatic Polypeptide / Q000378:metabolism*; D010477:Perfusion; D013004:Somatostatin / Q000494:pharmacology / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D013004:Somatostatin; D010191:Pancreatic Polypeptide; D005934:Glucagon