Copper-zinc superoxide dismutase is known to protect pancreatic beta-cell function from the damage of alloxan. A morphological investigation of copper-zinc superoxide dismutase prophylaxis against alloxan was undertaken in rats to investigate the mechanism of this protective action. Exogenous copper-zinc superoxide dismutase reproducibly protected the morphological features of pancreatic beta cells against damage by alloxan as determined by light microscopic immunostaining for insulin and by ultrastructural examination. By the same criteria, alpha and delta cells appeared unaffected by administration of a combination of alloxan and copper-zinc superoxide dismutase or either agent alone. Autoradiography after injection of 125I labelled copper-zinc superoxide dismutase into normal rats showed no evidence that the enzyme enters viable islet cells, suggesting an extracellular site of protection against alloxan.
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