Intraislet Somatostatin Inhibits Insulin (Via a Subtype-2 Somatostatin Receptor) but Not Islet Amyloid Polypeptide Secretion in the Isolated Perfused Human Pancreas

Azmi W. Atiya, Stephen Moldovan, Thomas E. Adrian, David Coy, John Walsh, F. Charles Brunicardi

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

It is our hypothesis that intraislet somatostatin regulates beta cell secretion in the isolated perfused human pancreas. The present study was designed to determine the relative influence of intraislet somatostatin on the regulation of islet amyloid polypeptide (IAPP) and insulin secretion, and to determine the effect of specific somatostatin receptor (SSTR) agonists on beta cell secretion during immunoneutralization of endogenous somatostatin in the isolated perfused human pancreas. Single-pass perfusion was performed in pancreata obtained from seven cadaveric organ donors using a modified Krebs medium with 3.9 mmol/L glucose. Sequential test periods were separated by basal periods and experiments were performed by infusion of any of the following: (1) somatostatin monoclonal antibody (S-Ab); (2) S-Ab + SSTR2 agonist (DC32-87); or (3) S-Ab + SSTR5 agonist (DC32-92). The changes in insulin and IAPP secretion from basal levels during each stimulation were calculated. Infusion of S-Ab resulted in a significant increase in insulin secretion (2033 ± 429 pmol/L; P <0.05) but not IAPP. In the presence of S-Ab, infusion of the SSTR2 agonist resulted in a significant inhibition of insulin secretion (-1128 ± 457 pmol/L; P <0.05) but not IAPP. In the presence of S-Ab, infusion of the SSTR5 agonist had no significant effect on insulin or IAPP secretion. We conclude that intraislet somatostatin inhibits insulin secretion via SSTR2, but not IAPP secretion, in the isolated perfused human pancreas model and that this effect occurs via SSTR2. These results also suggest that insulin and IAPP secretion are regulated by different mechanisms despite being co-localized to the beta cell.

Original languageEnglish
Pages (from-to)251-256
Number of pages6
JournalJournal of Gastrointestinal Surgery
Volume1
Issue number3
DOIs
Publication statusPublished - 1997
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Gastroenterology

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