IRON NITRILOTRIACETATE-INDUCED EXPERIMENTAL DIABETES IN RATS

Abstract

The etiology of diabetes in some conditions of Fe overload is not known. Growth, glucose tolerance and pancreatic islet cell morphology and cytochemistry were studied in rats administered parenteral FeNTA [ferric nitrilotriacetate]. These rats developed glucosuria, slowing of growth with eventual weight loss, polyuria, polydipsia and death. They had normal fasting plasma glucose levels but decreased glucose tolerance and insulin response to glucose. Although no Prussian blue staining of Fe was observed in pancreatic islets by light microscopy, at the ultrastructural level insulin-secreting .beta.-cells showed ferric iron deposits localized to the plasmalemma and the cytoplasmic surface of secretory granule membranes. Prussian blue staining was also observed in parenchymal cells of the liver, heart, and kidney, in order of decreasing intensity. Animals treated with an equivalent dose of NTA [nitriloacetate], saline, or iron-dextran in saline had normal growth and response to glucose and did not exhibit pancreatic Fe deposits at the light or ultrastructural level. Fe affects pancreatic islet cell function and may be an etiologic agent of diabetes mellitus in hemochromatosis.