Immunoneutralization of somatostatin, insulin, and glucagon causes alterations in islet cell secretion in the isolated perfused human pancreas

Pancreas. 2001 Oct;23(3):302-8. doi: 10.1097/00006676-200110000-00012.

Abstract

Introduction: In this study, immunoneutralization of endogenous insulin, glucagon, and somatostatin with specific antibodies was used in an isolated perfused human pancreas (IPHP) model.

Aims: To study intrapancreatic cellular interactions and pancreatic hormonal secretion.

Methodology: 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.

Conclusion: The variation in hormonal responses to immunoneutralization during stimulated and nonstimulated glucose conditions suggests that a dynamic association exists between the pancreatic cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Antibodies / pharmacology*
  • Antibodies, Monoclonal / pharmacology
  • Cadaver
  • Child
  • Female
  • Glucagon / immunology
  • Glucagon / metabolism*
  • Glucose / pharmacology
  • Humans
  • Insulin / immunology
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Male
  • Middle Aged
  • Models, Biological
  • Perfusion
  • Somatostatin / immunology
  • Somatostatin / metabolism*

Substances

  • Antibodies
  • Antibodies, Monoclonal
  • Insulin
  • Somatostatin
  • Glucagon
  • Glucose