Quantitative assessment of long-term changes in insulin secretion after canine duct-obliterated pancreas...

In this study, we have quantitatively assessed the changes in insulin-secreting capacity after duct-obliterated segmental pancreatic autotransplantation in dogs. To this end, we have used a technique for the sampling of the complete and undiluted pancreatic venous blood with simultaneous flow measurement, by which means the actual insulin-secreting capacity was determined in a direct fashion. Histologic changes were analyzed in addition in order to address the underlying mechanisms of the changes in insulin-secreting capacity. Intraoperative glucose-stimulated insulin secretion of the left pancreatic lobe was measured before (group I, n = 8), at 6 weeks (group II, n = 5), and at 18-24 months (group III, n = 7) after duct-obliterated segmental pancreatic autotransplantation. At all 3 intervals, histologic analysis was performed. Since the experiments in groups I-III were performed under general anesthesia, a 4th group of dogs (group IV, n = 6) was studied in addition in order to determine the effect of general anesthesia on glucose metabolism. K-values appeared to be reduced to 1/5 and peripheral insulin response (AUC) to about 1/3 of the values obtained from fasting conscious dogs. Although all animals in groups I-III had normal fasting glucose levels and normal K-values at each test interval, a 75% reduction of insulin secretion after duct-obliterated transplantation was observed. Insulin secretion not only showed marked quantitative changes but significant qualitative alterations in glucose-stimulated insulin response were found. Disturbance of functional islet architecture appears to be the main causative factor in the decrease in insulin secretion. If applicable to man, our results indicate that especially the duct-obliterated graft, with its borderline endocrine capacity, is prone to loss of sufficient graft function by the damage induced by eventual rejection crises.