Pathological analysis of cadmium and its microenvironment in patients with itai-itai disease

Cadmium (Cd) is a highly toxic heavy metal, which is widely dispersed in the environment. Itai-itai disease is well known as the most severe form of chronic Cd poisoning. We have examined the pathological findings of human samples in itai-itai disease, and reported the mechanism of kidney and bone failure. However it is not easy to detect cadmium localization on the tissue specimen. In present study, we performed EPMA (Electron Probe MicroAnalyser) analysis and succeeded to make clarify the cadmium toxicity in cellular level. Cadmium was accumulated in the hepatocytes, portal connective tissue in the liver, and residual proximal tubules and connective tissue in the kidney. In addition, cadmium was accumulated selectively in Langerhans islets of pancreas, surprisingly. Double immunostaining of insulin and glucagon suggested that marked deletion of beta cells in patients of itai-itai disease. we hypothesized that high dose cadmium exposure may be a risk of diabetes.