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

被引:16
作者
KLEINMAN, R
GINGERICH, R
WONG, H
WALSH, J
LLOYD, K
OHNING, G
DEGIORGIO, R
STERNINI, C
BRUNICARDI, FC
机构
[1] UNIV CALIF LOS ANGELES, CTR HLTH SCI, SCH MED, DEPT SURG, LOS ANGELES, CA 90024 USA
[2] VAMC W LOS ANGELES, DEPT SURG, LOS ANGELES, CA USA
[3] VAMC W LOS ANGELES, DEPT MED, LOS ANGELES, CA USA
[4] VAMC W LOS ANGELES, CURE, LOS ANGELES, CA USA
[5] WASHINGTON UNIV, SCH MED, DEPT PEDIAT, ST LOUIS, MO 63110 USA
关键词
D O I
10.1016/0002-9610(94)90061-2
中图分类号
R61 [外科手术学];
学科分类号
摘要
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-IP 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 Feb 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.
引用
收藏
页码:114 / 119
页数:6
相关论文
共 29 条
  • [1] DOSE-RESPONSE EFFECT OF SOMATOSTATIN-14 ON HUMAN BASAL PANCREATIC HORMONES
    ANNIBALE, B
    DELLEFAVE, G
    BARBETTI, F
    DEMAGISTRIS, L
    PUOTI, M
    GIORDANO, E
    LEONETTI, F
    TAMBURRANO, G
    [J]. PANCREAS, 1987, 2 (05) : 551 - 556
  • [2] 3-DIMENSIONAL IMAGING OF INTACT ISOLATED ISLETS OF LANGERHANS WITH CONFOCAL MICROSCOPY
    BRELJE, TC
    SCHARP, DW
    SORENSON, RL
    [J]. DIABETES, 1989, 38 (06) : 808 - 814
  • [3] SELECTIVE NEUROHORMONAL INTERACTIONS IN ISLET CELL SECRETION IN THE ISOLATED PERFUSED HUMAN PANCREAS
    BRUNICARDI, FC
    DRUCK, P
    SEYMOUR, NE
    SUN, YS
    ELAHI, D
    ANDERSEN, DK
    [J]. JOURNAL OF SURGICAL RESEARCH, 1990, 48 (04) : 273 - 278
  • [4] AN IMMUNOCYTOCHEMICAL INVESTIGATION WITH MONOCLONAL-ANTIBODIES TO SOMATOSTATIN
    BUCHAN, AMJ
    SIKORA, LKJ
    LEVY, JG
    MCINTOSH, CHS
    DYCK, I
    BROWN, JC
    [J]. HISTOCHEMISTRY, 1985, 83 (02) : 175 - 180
  • [5] CULLER MD, 1980, METHOD ENZYMOL, V168, P498
  • [6] TISSUE DISTRIBUTION AND INNERVATION PATTERN OF PEPTIDE IMMUNOREACTIVITIES IN THE RAT PANCREAS
    DEGIORGIO, R
    STERNINI, C
    ANDERSON, K
    BRECHA, NC
    GO, VLW
    [J]. PEPTIDES, 1992, 13 (01) : 91 - 98
  • [7] ELSHAMI AS, 1983, CLIN CHEM, V29, P1170
  • [8] SOMATOSTATIN RESTRAINT OF GASTRIN-SECRETION IN PIGS REVEALED BY MONOCLONAL-ANTIBODY IMMUNONEUTRALIZATION
    HOLST, JJ
    JORGENSEN, PN
    RASMUSSEN, TN
    SCHMIDT, P
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1992, 263 (06): : G908 - G912
  • [9] ANTISOMATOSTATIN GAMMA-GLOBULIN AUGMENTS SECRETION OF BOTH INSULIN AND GLUCAGON INVITRO - EVIDENCE FOR A PHYSIOLOGIC ROLE FOR ENDOGENOUS SOMATOSTATIN IN THE REGULATION OF PANCREATIC A-CELL AND B-CELL FUNCTION
    ITOH, M
    MANDARINO, L
    GERICH, JE
    [J]. DIABETES, 1980, 29 (09) : 693 - 696
  • [10] KLEINMAN R, IN PRESS PANCREAS