USE OF THE FAB FRAGMENT FOR IMMUNONEUTRALIZATION OF SOMATOSTATIN IN THE ISOLATED-PERFUSED HUMAN PANCREAS

The role of the somatostatin-secreting D cell in the islet remains con troversial. The present study was undertaken to determine whether infu sion of the Fab fragment of a highly sensitive somatostatin monoclonal antibody into the isolated, perfused human pancreas would influence i nsulin secretion. Single-pass perfusion was performed in pancreata obt ained 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 (S Fab), somatostatin-14 (SS-14), or a combined infusion. Immunoneutraliz ation of intraislet somatostatin with SFab resulted in a significant i ncrease 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 secreti on (-3,372 +/- 1,360 pM) (p < 0.05) and IRC-P secretion (-708 +/- 220 pM) (p < 0.05). Combined infusion of SFab and SS-IP reversed the inhib itory effect of exogenous SS-14 on IRI and IRC-P secretion. The data s uggest that intraislet somatostatin has an inhibitory role in the regu lation of B-cell secretion in the human islet and demonstrates that th e Feb fragment of the somatostatin monoclonal antibody is an effective tool for immunoneutralization studies in the human pancreas. In addit ion, immunostaining of the donor pancreata demonstrated the presence o f 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 th e concept that intraislet somatostatin influences insulin secretion in the human islet.