Use of the fab fragment for immimoneutralization of somatostatin in the isolated perfused human pancreas

Robert Kleinman, Ron Gingerich, Helen Wong, John Walsh, Kevin C K Lloyd, Gordon Ohning, Roberto De Giorgio, Catia Sternini, F. Charles Brunicardi

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The role of the somatostatin-secreting D cell in the islet remains controversial. The present study was undertaken to determine whether infusion of the Fab fragment of a highly sensitive somatostatin monoclonal antibody into the isolated, perfused human pancreas would influence insulin secretion. Single-pass perfusion was performed in pancreata obtained from cadaveric organ donors using a modified Krebs-media with 3.9 mM glucose. Sequential test periods separated by basal periods were performed with either somatostatin monoclonal antibody Fab fragment (SFab), somatostatin-14 (SS-14), or a combined infusion. Immunoneutralization of intraislet somatostatin with SFab resulted in a significant increase in both immunoreactive insulin (IRI) (1,122 ± 497 pM) (p <0.05) and immunoreactive C-peptide (IRC-P) secretion (146 ± 53 pM) (p <0.05). Infusion of SS-14 resulted in inhibition of both IRI secretion (-3,372 ± 1,360 pM) (p <0.05) and IRC-P secretion (-708 ±220 pM) (p <0.05). Combined infusion of SFab and SS-14 reversed the inhibitory effect of exogenous SS-14 on IRI and IRC-P secretion. The data suggest that intraislet somatostatin has an inhibitory role in the regulation of B-cell secretion in the human islet and demonstrates that the Fab fragment of the somatostatin monoclonal antibody is an effective tool for immunoneutralization studies in the human pancreas. In addition, immunostaining of the donor pancreata demonstrated the presence of somatostatin-immunoreactive endocrine cells interspersed throughout the islet core and mantle. The demonstrated proximity of somatostatin-immunoreactive endocrine cells to B cells lends anatomic support to the concept that intraislet somatostatin influences insulin secretion in the human islet.

Original languageEnglish (US)
Pages (from-to)114-119
Number of pages6
JournalThe American Journal of Surgery
Volume167
Issue number1
DOIs
StatePublished - 1994

ASJC Scopus subject areas

  • Surgery

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    Kleinman, R., Gingerich, R., Wong, H., Walsh, J., Lloyd, K. C. K., Ohning, G., De Giorgio, R., Sternini, C., & Brunicardi, F. C. (1994). Use of the fab fragment for immimoneutralization of somatostatin in the isolated perfused human pancreas. The American Journal of Surgery, 167(1), 114-119. https://doi.org/10.1016/0002-9610(94)90061-2