EFFECT OF SULFHYDRYL-BINDING REAGENTS ON ISLET TISSUE PERMEABILITY: PROTECTION AND REVERSAL BY THIOL COMPOUNDS

¹ Department of Anatomy, University of Connecticut Schools of Medicine and Dental Medicine, Farmington, Connecticut; Department of Anatomy, University of Minnesota School of Medicine, Minneapolis, Minnesota; Marine Biological Laboratory, Woods Hole, Massachusetts

The ability of various thiol compounds to protect against and reverse the action of alloxan and other sulfhydryl-binding reagents on islet tissue permeability was studied. When islet slices were preincubated in alloxan, washed and incubated in d-mannitol-1-C¹⁴ (which does not normally penetrate cells), the amount of C¹⁴ in the tissue was increased as a result of the alloxan-induced damage to the cell membranes. Pretreatment of the tissue with 2,3-dimercaptopropanol (BAL), glutathione (GSH) or cysteine before treatment with alloxan completely protected the slices against the action of alloxan. In contrast, when islet slices were first preincubated in alloxan and then preincubated in the thiol compound, only the dithiol, BAL, reversed the effect. Similar results were obtained with a number of dithiol-binding reagents (Co⁺⁺, Hg⁺⁺, AsO₂^- and dichlorophenylarsine), whereas Cd⁺⁺ differed in that GSH also partially reversed its effect. The results obtained with the alkylating reagent, N-ethylmaleimide, were similar to those obtained with the dithiol-binding reagents; however, another alkylating reagent, iodoacetic acid, differed in that GSH did not protect the islets from its action and BAL only partially reversed its effect. When the oxidizing reagents, oxidized glutathione and cystine, were used, both GSH and BAL completely reversed their effect. Since GSH reversed the effect of oxidized glutathione but not that of ailoxan, the reaction of alloxan with the membrane sulfhydryl groups probably involves more than simple oxidation of SH groups to the disulfide form.