The influence of somatostatin on glucagon and pancreatic polypeptide secretion in the isolated perfused human pancreas |
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Authors: | Robert Kleinman Ronald Gingerich Gordon Ohning Helen Wong Kim Olthoff John Walsh F. Charles Brunicardi |
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Affiliation: | (1) The Departments of Surgery, Medicine, and CURE, VAMC-West Los Angeles, Los Angeles, CA;(2) the Department of Surgery, UCLA School of Medicine, Los Angeles, CA;(3) the Department of Pediatrics, Washington University School of Medicine, St. Louis, MO;(4) Room 72-244 CHS, UCLA Center for the Health Sciences, 10833 Le Conte Ave., 90095-6904 Los Angeles, CA |
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Abstract: | Summary 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 (ΔX=15±3 pM) (p<0.05), but did not significantly effect glucagon secretion under high-glucose conditions (ΔX=−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. |
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Keywords: | Isolated perfused pancreas somatostatin human glucagon pancreatic polypeptide |
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