Influence of sex, strain, and species on trace metal status of insulin-deficient diabetic rodents.

Previous studies have demonstrated marked alterations in trace metal metabolism in male Sprague-Dawley rats following chemical induction of the diabetic state. To determine whether such changes represented a general response to the insulin-deficient condition the levels of zinc, copper, and maganese in liver, kidney, and intestine of normal and streptozotocin (STZ)-diabetic male rats of the Sprague-Dawley, Wistar, and Long-Evans strains, female Sprague-Dawley rats, and male mice were measured. Significantly increased concentrations of zinc, copper, and maganese in liver, and zinc and copper in kidney were found in STZ-diabetic rats, regardless of sex and strain. In contrast, the zinc and copper contents in liver and kidney of control and STZ-diabetic mice were similar, but hepatic manganese levels were significantly elevated in both organs of the diabetic mouse. The concentrations of all three metals were similar in the intestine of control and diabetic rodents. Higher amounts of zinc and copper were bound to metallothionein in the liver and kidney of the diabetic rats. Nicotinamide injection prior to STZ administration protected rats against the development of diabetes and alterations in trace metal status. These data indicate that specific alterations in the metabolism of zinc, copper and manganese during episodes of pancreatic hormonal imbalance represent a general phenomenon in the rat. A possible explanation for the differential response of the STZ-diabetic mouse is discussed.