Ex Vivo Evaluation in Normal Dogs of Insulin Released by a Bioartificial Pancreas Containing Isolated Rat Islets of Langerhans

Abstract: In bioartificial pancreatic systems, isolated islets of Langerhans are protected against immune rejection by an artificial membrane, permeable to glucose and insulin, but not to immunoglobulins and lymphocytes. Some of these devices, referred to as vascular systems, are set up to be connected to a vascular site in the recipient, with blood circulating in contact with one side of the membrane, and the islets on the other side. Such a bioartificial pancreas, containing isolated rat islets of Langerhans, was connected to an arteriovenous shunt of a normal anesthetized dog. The aim of this experiment was to investigate the kinetics of the insulin secretory response of the system to a glucose load. Glucose was infused upstream of the system, increasing the glucose concentration inside the bioartificial pancreas from 7 to 14 mmol/1, without altering the blood glucose concentration of the dog. Insulin concentration was determined simultaneously upstream and downstream of the bioartificial pancreas. Insulin production was calculated by multiplying the difference between these values by the blood flow rate. Blood flow rate (Q) was estimated from the change in the glucose concentration produced by the glucose infusion using a mass transfer analysis derived from Fick's principle. Insulin production increased from 20 ± 8 to 59 ± 15 μU/100 islets/min within 15 min following the beginning of the stimulation (n = 6, p < 0.05). Five min after the end of the stimulation, insulin production decreased from 75 ± 13 to 50 ± 9 μU/100 islets/min (p < 0.05) to reach the basal level (21 ± 3 μU/100 islets/min) 30 min after the end of the glucose stimulation. This rapid response to changes in blood glucose concentration, demonstrated ex vivo with the device connected directly to an arterial vessel, is consistent with the establishment of closed-loop insulin delivery by this bioartificial pancreas.