To assess the effects of artificial beta-cell-directed insulin therapy on protein metabolism in patients with diabetes mellitus, nitrogen balance, urea production, and whole body protein turnover were determined in five type I insulin-dependent subjects and five age- and sex-matched controls. Each diabetic participant was studied over two 4-day periods while receiving conventional insulin therapy (one or two daily injections of short and intermediate acting insulin) or insulin delivered by the artificial beta-cell. While the diabetic participants received conventional insulin therapy, nitrogen balance, urea production, whole body protein turnover, and protein synthesis and breakdown rates did not differ significantly from the control group. However, when the same subjects were on artificial beta-cell-directed insulin therapy, they manifested a significant net positive nitrogen balance of over 2 g/day. This change in nitrogen balance was largely due to a fall in urea nitrogen production from 174 +/- 6 to 140 +/- 13 mg/kg body weight per day (p less than 0.05). In addition, while artificial beta-cell therapy did not affect whole body protein turnover or breakdown rates, a significant rise (2.1 +/- 0.2 to 2.4 +/- 0.1 g/kg per day) in whole body protein synthesis was observed (p less than 0.05). Thus when compared to conventional insulin treatment, artificial beta-cell-directed insulin therapy was associated with a 14% increase in the rate of protein synthesis and a decrease of 20% in urea nitrogen production, leading to a net positive nitrogen balance.