Determinants of the selective toxicity of alloxan to the pancreatic B cell.

The diabetogenic agent alloxan exerts a preferential cytotoxic effect on the pancreatic B cell. The determinants of such a tissue specificity were investigated. Alloxan accumulated rapidly in liver and pancreatic islets but much more slowly in muscle. The activity of glutathione peroxidase and the resistance to exogenous peroxide were approximately 20 times higher in liver and kidney than in islets, intermediate values being found in exocrine pancreas and muscle. These findings suggest that the selective cytotoxicity of alloxan to the pancreatic B cell is attributable to the conjunction of two features: a rapid cellular uptake of the drug and an exquisite sensitivity of the B cell to peroxide.