Immunoneutralization of Somatostatin, Insulin, and Glucagon Causes Alterations in Islet Cell Secretion in the Isolated Perfused Human Pancreas

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IntroductionIn this study, immunoneutralization of endogenous insulin, glucagon, and somatostatin with specific antibodies was used in an isolated perfused human pancreas (IPHP) model.AimsTo study intrapancreatic cellular interactions and pancreatic hormonal secretion.MethodologyRandomized, sequential 10-minute test intervals of single-pass perfusion with each antibody were performed at 3.9 m M or 11.5 m M steady-state glucose concentrations. Somatostatin, insulin, and glucagon levels were measured in the effluent during basal and immunoneutralization intervals.ResultsAt 3.9 m M 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 m M glucose concentration, SS-Ab stimulated insulin secretion, IN-Ab stimulated glucagon and inhibited somatostatin secretion, and GN-Ab stimulated insulin secretion.ConclusionThe variation in hormonal responses to immunoneutralization during stimulated and nonstimulated glucose conditions suggests that a dynamic association exists between the pancreatic cells.

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