Ex vivo evaluation in normal dogs of insulin released by a bioartificial pancreas containing isolated rat islets of Langerhans.

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/l, 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 microU/100 islets/min within 15 min following the beginning of the stimulation (n = 6, p less than 0.05). Five min after the end of the stimulation, insulin production decreased from 75 +/- 13 to 50 +/- 9 microU/100 islets/min (p less than 0.05) to reach the basal level (21 +/- 3 microU/100 islets/min) 30 min after the end of the glucose stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro evaluation of a bioartificial pancreas under various hemodynamic conditions.

A bioartificial pancreas in which isolated islets of Langerhans are placed between two polyacrylonitrile membranes, blood circulating successively above the upper and below the lower membranes following a U-shaped circuit, has been developed. The two parts are connected by an outer loop consisting of a thin tubing. The length of this tubing determines the magnitude of the flow rate of blood through the device. The aim of this work was to determine experimentally the optimal configuration of the system containing isolated rat islets and a Krebs buffer circulating through the device. The amount of insulin released by the bioartificial pancreas was determined during a 20-mM square-wave glucose stimulation. First, the inlet pressure was set at 100 mm Hg, and the effect of the length of the tubing was investigated with two devices perfused simultaneously. For a short tubing (flow rate, 20 ml/min), a sharp increase in insulin release in response to glucose was observed; it increased within 4 min from 217 +/- 50 to 761 +/- 237 microU/500 islets/min (p less than 0.05), the peak value being reached at 11 +/- 2 min following the beginning of the stimulation. For a long tubing (flow rate, 3 ml/min), the increase in insulin release was more sluggish. It increased from 133 +/- 53 to 222 +/- 43 microU/500 islets/min at 4 min, the peak value being reached only at 20 +/- 3 min. These data are consistent with a more efficient diffusional transfer of insulin in the case of the high circulating flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Portal versus peripheral venous drainage in segmental pancreatic transplantation in diabetic rats.

The effect of the site of venous drainage in segmental pancreatic transplantation was investigated in diabetic rats with two surgical procedures anastomosing the superior mesenteric vein either on the vena cava (systemic drainage) or on the superior mesenteric vein (portal drainage). Both procedures corrected polyuria, glycosuria, and blood glucose concentration, and resulted in similar peripheral hyperinsulinemia. Intravenous glucose tolerance tests were performed 8 weeks after transplantation. In portal-grafted rats, glucose tolerance was strictly normalized, with a plasma insulin profile similar to that observed in normal rats. In caval-grafted rats, a delayed plasma insulin peak was observed with slight abnormalities in the plasma glucose profile, the late plasma glucose concentrations being higher than in portal-grafted animals. The extent of fibrosis was similar under both conditions. This study, performed in rats, of the influence of venous drainage on the metabolic outcome of segmental transplantation, demonstrating an abnormal plasma insulin profile during a glucose challenge in case of caval drainage, is consistent with other studies suggesting that the site of drainage might be important in case of reduced grafted mass.

[Role of the digestive tract immune system in the control of bacterial translocation in gnotoxenic mice]. / Rôle du système immunitaire digestif dans le contrôle de la translocation bactérienne chez la souris gnotoxénique.

The aim of this work was to study the role of gut associated lymphoid tissue in the control of bacterial translocation. Two strains of Escherichia coli were orally inoculated to 71 axenic mice. Ten days after, the 2 initial strains and 2 others, resulting from plasmidic exchanges, were present in the digestive tract of the mice which were divided in two groups: the first group (n = 41) received one intraperitoneal injection of cyclophosphamide 100 mg/kg; the second control group (n = 30) received isotonic saline. The following parameters were studied 3, 5 and 9 days after the injection: the population level of the 4 strains in the caecum, their translocation to mesenteric lymph nodes, liver, spleen and circulating blood, the density per unit surface of lamina propria plasma cells and intraepithelial lymphocytes in duodenal and caecal mucosae. The population in each strain found in the caecum was different from the 3 others but similar within the two groups of animals and remained unchanged with time. In the control group, bacterial translocation to the mesenteric lymph nodes decreased (p less than 0.01), while the density of plasma cells increased (p less than 0.01) from the 3rd to the 9th days. In the cyclophosphamide treated group, translocation to the mesenteric lymph nodes increased (p less than 0.01), while the density of intestinal plasma cells decreased (p less than 0.05) from the 3rd to the 9th days. Density of intraepithelial lymphocytes did not vary with time in each group and from one group to another. Bacterial translocation to liver, spleen and systemic blood was weak and did not increase in the treated group.(ABSTRACT TRUNCATED AT 250 WORDS)