Effect of alloxan on permeability of pancreatic islet tissue in vitro

¹ Department of Anatomy, Western Reserve University School of Medicine, Cleveland, Ohio; Department of Anatomy, University of Minnesota School of Medicine, Minneapolis, Minnesota; and Marine Biological Laboratory, Woods Hole, Massachusetts

The effect of alloxan on the permeability of toadfish islet slices was studied in vitro at 0 C, pH 7.0. When islet slices were incubated in d-mannitol-1-C¹⁴, a compound which does not enter cells, the C¹⁴ content of the slice reached 30% of that of the medium. In the presence of 2.5 x 10^–4 m unlabeled alloxan (a concentration which may be present following injection of a diabetogenic dose), the C¹⁴ content of the tissue increased to about 50%. Alloxan also increased the loss of protein and insulin from the islet. This effect was specific for islet; higher concentrations of alloxan had no effect on any other tissue tested. Alloxanic acid, the nondiabetogenic decomposition product of alloxan, had no effect. p-Hydroxymercuribenzoate did not affect permeability but it potentiated the action of alloxan. Pretreatment of islet slices with glutathione or cysteine protected them against the subsequent action of alloxan; however, treatment with these agents after treatment with alloxan did not reverse the alloxan effect. These results suggest that alloxan may exert its diabetogenic effect by damaging the ß-cell membrane, thereby increasing its permeability.

Key Words: alloxan diabetes • ßbeta; cell • cell membrane • extracellular space • diabetes • cytotoxin • sulfhydryl reagents • glutathione • alloxan, mechanism of action

Submitted on November 7, 1963