Immunoneutralization of somatostatin, insulin, and glucagon causes alterations in islet cell secretion in the isolated perfused human pancreas.
BACKGROUND
In this study, immunoneutralization of endogenous insulin, glucagon, and somatostatin with specific antibodies was used in an isolated perfused human pancreas (IPHP) model.


OBJECTIVE
To study intrapancreatic cellular interactions and pancreatic hormonal secretion.


METHODS
Randomized, sequential 10-minute test intervals of single-pass perfusion with each antibody were performed at 3.9 mM or 11.5 mM steady-state glucose concentrations. Somatostatin, insulin, and glucagon levels were measured in the effluent during basal and immunoneutralization intervals.


RESULTS
At 3.9 mM glucose concentration, somatostatin antibody (SS-Ab) stimulated insulin and glucagon secretion, insulin antibody (IN-Ab) inhibited glucagon secretion, and glucagon antibody (GN-Ab) stimulated insulin secretion. At 11.5 mM glucose concentration, SS-Ab stimulated insulin secretion, IN-Ab stimulated glucagon and inhibited somatostatin secretion, and GN-Ab stimulated insulin secretion.


CONCLUSIONS
The variation in hormonal responses to immunoneutralization during stimulated and nonstimulated glucose conditions suggests that a dynamic association exists between the pancreatic cells.
Brunicardi
F C
FC
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.
Kleinman
R
R
Moldovan
S
S
Nguyen
T H
TH
Watt
P C
PC
Walsh
J
J
Gingerich
R
R
D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002102:Cadaver; D002648:Child; D005260:Female; D005934:Glucagon / Q000276:immunology / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000276:immunology / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010477:Perfusion; D013004:Somatostatin / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D007328:Insulin; D013004:Somatostatin; D005934:Glucagon; D005947:Glucose