IMMUNOLOGICAL AND INSULIN SECRETORY STUDIES ON ISOLATED PORCINE ISLETS OF LANGERHANS

Since porcine islets are considered a likely tissue source for islet transplantation we have studied the insulin secretory responses to stimuli and some of the cell surface antigen characteristics of porcine islet cells. In a static incubation system, the threshold level of glucose required for the stimulation of insulin secretion from freshly isolated porcine islets was found to be between 2.8 and 4.2 mmol glucose/l. Arginine (5 mmol/l) and 3-isobutyl-1-methylxanthine (1 mmol/l) potentiated insulin release induced by 8.3 mmol glucose/l. Leucine (5 mmol/l) initiated release in the presence of 2 mmol glucose/l. Neither β-hydroxybutyrate (10 mmol/l) nor octanoate (5 mmol/l) potentiated insulin release induced by 8.3 mmol glucose/l, but β-hydroxybutyrate initiated release in the presence of 2 mmol glucose/l while octanoate did not. A 125I-labelled protein A binding assay and an enzyme-linked immunosorbent assay system were used to detect antibody binding to islet and non-islet cells. Monoclonal antibodies raised against intact rat islets were shown to bind to both porcine and rat islet cells, but not to rat hepatoma tissue culture cells or rat insulinoma cells. The serum from recently diagnosed type I diabetics was shown to bind to rat islet cells in a 125I-labelled protein A binding assay, while serum from control subjects showed little, if any, binding. Porcine islet cells were unable to distinguish between the sera of recently diagnosed type I diabetics and controls in a similar assay. In conclusion, porcine islets respond to many of the major insulin secretagogues to which human islets are sensitive. However, they have a lower secretory response to these compounds compared with that reported for human islets. Monoclonal antibody and human sera binding studies show that rat and porcine islets share some cell surface antigens but it remains to be seen whether the inability of porcine islets to discriminate between diabetic and non-diabetic sera is an advantage for transplantation, indicating less likelihood of an islet-specific autoimmune-like humoral attack.