Pancreatic islets after repeated injection of Fe3+-NTA. An ultrastructural study of diabetic rats.

Pancreatic islet cells were examined ultrastructurally in rats after repeated intraperitoneal injections of ferric nitrilotriacetate (Fe3+-NTA) to produce a model of bronze diabetes. Despite diabetic signs such as glycosuria and ketouria, no ultrastructural alterations were found in islet cells up to 90 days after the beginning of the Fe3+-NTA injections. After 120 days, however, degenerative changes appeared, with most B cells of the islets of Langerhans showing clumped nuclear chromatin, a dilated nuclear envelope, vacuolated and dilated endoplasmic reticulum, and a loss of cell polarization toward the capillary lumen. The cells contained a number of light secretory granules with an electron-lucent core and a narrow halo. Numerous electron-dense ferritin-like particles were also found in the cytoplasmic matrix, and A and D cells were almost intact. Repeated venesection therapy of rats injected with Fe3+-NTA for 120 days resulted in an increase of morphologically normal B cells with a smaller number of necrotizing cells. This process was accompanied by recovery from diabetic symptoms. The toxic effect of injected iron on B cells was thus clarified.