To assess the change in glucose handling capability of diabetic patients regulated with an artificial beta-cell, five insulin-dependent diabetic subjects were challenged with a 100-g glucose meal while on conventional (*single or split mixed insulin injections) therapy and again after 72 h on an artificial beta-cell unit. It was determined that while receiving conventional therapy, the diabetic patient's capacity to oxidize glucose was severely impaired. In addition, glucose storage was markedly reduced. After 72 h on the artificial beta-cell unit, the diabetic patient's capacity to oxidize glucose following the ingestion of the glucose meal significantly exceeded that of the control group, and glucose storage returned to normal. Since the above study did not reveal the amount of time on the artificial beta-cell required to restore the glucose processing capability of the diabetic patients to normal, their response to a mixed test meal ingested at noon was monitored while they were on conventional insulin therapy and during four consecutive days that they were on the artificial beta-cell. This inquiry revealed a gradual increase in their capacity to oxidize carbohydrate in response to the test meal. In contrast, their ability to store carbohydrate was normalized within 24 h following initiation of artificial beta-cell therapy. These studies clearly reveal that the conventionally treated diabetic patient's capacity to both oxidize and store carbohydrate is severely impaired. Both functions can be restored to normal by the use of the artificial beta-cell for 48-72 h. Most importantly, the gradual improvement in carbohydrate oxidation with respect to the daily mixed meal challenge suggests that it is an "inducible" process which requires at least 2-3 days to accomplish. Since the ability to both oxidize and store incoming carbohydrate is essential for glucose homeostasis, these observations may have significant implications for the care of diabetic patients.

A B S T R A C T The role of muscle in the processing of dietary carbohydrate in nine type I diabetic patients was assessed using combined forearm-indirect calorimetry-glucose meal (100 g) studies performed before and after 72 h of artificial 13-cell directed insulin therapy. On conventional insulin therapy, initially elevated arterial glucose concentrations rose markedly, free insulin increased slightly, and the respiratory quotient (R.Q.) did not change during the study. The forearm glucose extraction rate increased significantly over basal at 60 min. After 72 h of artificial ,3-cell therapy and while still on the instrument, arterial glucose increased moderately, and free insulin levels increased markedly. The R.Q. increased significantly at 60 and 120 min. The forearm glucose extraction rate increased significantly over basal at 30 and 60 min. Importantly, forearm glucose extraction rates did not differ during the two studies at each of the measured time points. These observations demonstrate that conventional insulin therapy is effective in facilitating glucose entry into muscle. In addition, they suggest that the marked improvement in glucose processing exhibited by type

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.