Role of the Secretion Vesicle in the Transport of Receptors: Modulation of Somatostatin Binding to Pancreatic Islets*

Publisher Website
Google Scholar
Abstract
Glucose augments islet somatostatin binding by increasing receptor concentration with no change in receptor affinity. The increased binding of somatostatin could be due to 1) de novo receptor synthesis, 2) decrease in the rate of receptor internalization, or 3) translocation of receptors from the Golgi apparatus to the plasma membrane during emiocytosis. Studies were undertaken to test these three possibilities. A dose of cycloheximide (1 mM) sufficient to produce an 81 ± 2% decrease in protein synthesis did not inhibit the increased somatostatin binding induced by 16.7 mM glucose. Internalization of ligand-receptor complex was indirectly assessed by incubating islets with [125I]iodosomatostatin (pH 7.4) in order to measure total cell binding and then treating them with 0.2 N acetic acid (pH 2.5) to remove cell surface bound somatostatin and determine residual intracellular radioactivity. The acetic acid treatment results in dissociation of the ligandsurface receptor complex. Residual radioactivity reflects internalized ligand and in the case of receptor-mediated internalization, provides an indirect measurement of receptor internalization. Under these conditions, exposing islets to high glucose concentrations did not result in a decrease in the amount of internalized ligand. In fact, the magnitude of internalized ligand appeared to be significantly increased, probably due in part to the increase in cell surface somatostatin receptor concentration seen with 16.7 mM glucose. When glucose-exposed islets were incubated with [125I]iodosomatostatin at 4 C, internalization of ligand was restricted, and enhanced somatostatin binding was still observed with high glucose concentrations. Islets were perifused at two glucose concentrations (1.67 and 16.7 mM) in the presence of 1 mM colchicine, a known inhibitor of microtubule function. Colchicine interfered with the second phase of glucose-stimulated insulin release and total insulin output was inhibited 47 ± 3%. Concomitantly, the increase in somatostatin binding observed with 16.7 mM glucose was suppressed 57.8 ± 9.3%. Incubation of islets with deuterium oxide in like manner resulted in inhibition of the increase in somatostatin binding and insulin release produced by 16.7 mM glucose. It appears therefore that a critical event in the modulation of surface membrane somatostatin receptor concentration is the migration of the secretion vesicle during emiocytosis, which thereby promotes increased transport of somatostatin receptors.

This publication has 0 references indexed in Scilit: