Induction of diabetes in animals by parenteral administration of ferric nitrilotriacetate. A model of experimental hemochromatosis.

Rats and rabbits parenterally treated with a large daily dose of ferric nitrilotriacetate manifested diabetic symptoms such as hypergycemia, glycosuria, ketonemia, and ketonuria after approximately 60 days fo treatment. The blood insulin response to oral glucose loading was poor. Heavy iron deposits were found in liver parenchymal cells and in pancreatic exocrine cells, although some iron was deposited in the macrophages and reticuloendothelial cells of the organs. Faint iron staining was found in some pancreatic islet cells, with a reduction in beta granules and weak zinc staining. Cirrhotic liver changes and skin pigment deposition were not observed. Repeated blood withdrawals from ferric-nitrilotriacetate-treated animals resulted in disappearance of hypergycmia, glycosuria, ketonemia, and ketonuria; disappearance of iron from the liver and pancreas; and restoration of islet beta granules to the control level.