Abstract

The effects of N-iodoacetyl-2-amino-2-deoxy-D-glucose and various N-bromoacetylglycosylamines on the release of insulin from microdissected pancreatic islets of non-inbred ob/ob mice were studied. N-Bromoacetyl-β-D-glucosylamine (10 mM) initiated insulin release in the absence of D-glucose and, at concentrations of 2.5-10 mM, but not 20 mM, potentiated insulin release in response to 10 mM D-glucose. The potentiating, but not the initiating, action was significantly inhibited in the presence of mannoheptulose. N-Bromoacetyl-β-L-glucosylamine or N-bromoacetyl-β-D-galactosylamine had no effect in the absence of D-glucose. However, 2.5-20 mM concentrations of the L-glucose derivative and 1.25-5.0 mM concentrations of the D-galactose derivative potentiated the effect of 10 mM D-glucose; at 20 mM the D-galactose derivative inhibited the D-glucose-induced insulin release. N-Iodoacetyl-2-amino-2-deoxy-D-glucose (0.1-10 mM) did not initiate or potentiate insulin release but, at a concentration of 10 mM, inhibited the effect of D-glucose. The results support our hypothesis that alkylation of thiol groups in the β-cell plasma membrane leads to potentiation of D-glucose-induced insulin release if glycolysis is not simultaneously inhibited by the thiol reagent. If a regulatory site ("direct receptor") for the D-glucose molecule plays a role in stimulus recognition, N-iodoacetyl-2-amino-2-deoxy-D-glucose may be valuable in attempts to label and isolate it.