The pancreatic β cell recognition of insulin secretagogues. XII. Insulin release in response to halogenated hexosamines
Summary, in English
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 m(M)) initiated insulin release in the absence of (D) glucose and, at concentrations of 2.5-10 m(M), but not 20 m(M), potentiated insulin release in response to 10 m(M) (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 m(M) concentrations of the (L) glucose derivative and 1.25-5.0 m(M) concentrations of the (D) galactose derivative potentiated the effect of 10 m(M) (D) glucose; at 20 m(M) the (D) galactose derivative inhibited the (D) glucose induced insulin release. N Iodoacetyl 2 amino 2 deoxy (D) glucose (0.1-10 m(M)) did not initiate or potentiate insulin release but, at a concentration of 10 m(M), inhibited the effect of (D) glucose. The results support this 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.
American Society for Pharmacology and Experimental Therapeutics
- ISSN: 0026-895X