The bioessential trace metals (e.g. zinc, copper and iron) are primarily excreted via the gastrointestinal trace in normal man and animals. Although urinary losses of these trace metals are usually minimal, they have been reported to be markedly elevated during periods of physiological and pathological stress. The possibility that the decreased plasma insulin to glucagon ratio during episodes of stress is responsible for increased urinary trace metal excretion was examined in normal and streptozotocin-diabetic rats. Induction of the diabetic condition resulted in a rapid and persistent increase in the quantities of zinc, copper and iron lost in the urine daily. Diabetic rats excreted 3.4, 5.0, and 4.9-fold more zinc, copper and iron, respectively, at 14 days after injection with the diabetogenic drug than the controls. Insulin treatment of diabetic rats significantly reduced the daily urinary losses of these micronutrients, indicating that altered hormonal balance was the primary cause for elevated urinary excretion. Enhanced urinary losses of these metals were not associated with decreased concentrations of zinc, copper and iron in plasma, liver and kidney. Various processes, including the filterability of the metal, glomerular filtration rate, renal tubular reabsorption and transtubular secretion have been reported to influence urinary excretion of trace metals. Initial studies have been conducted to assess the influence of altered endocrine status on the characteristics of zinc binding and transport by renal brush border membrane vesicles (BBMV) in vitro. The accumulation of zinc by BBMV was found to be temperature dependent. No apparent differences in the binding and intravesicular accumulation of zinc by brush border membrane vesicles prepared from normal and STZ-diabetic rats were observed. Likewise, the efflux of zinc from BBMV prepared from control and diabetic renal cortex was similar. These results indicated that the potential for zinc reabsorption is not altered in the diabetic rats. In vivo studies are required to further assess the characteristics of zinc reabsorption in the native milieu. / M.S.