PANCREATIC TRANSPLANTATION REVERSES ENDOTHELIAL DYSFUNCTION IN EXPERIMENTAL DIABETES-MELLITUS

Background. There is insufficient evidence whether transplantation of the whole pancreas can reverse vascular complications associated with diabetes. In this study we investigated whether pancreatic transplanta tion in experimental diabetes reverses established defects in endothel ium-dependent relaxation. Methods. Streptozotocin-induced diabetic rat s underwent whole-pancreas transplantation after 12 weeks of disease. Endothelial function was evaluated 4 weeks after transplantation and c ompared with that of control- and age-matched diabetic animals. Blood was taken for analysis of glucose, insulin, total glycosylated hemoglo bin, and plasma amino acid levels. Descending thoracic aortas were iso lated, sectioned into rings, and mounted in isolated tissue baths. In precontracted rings, endothelium-dependent relaxation to acetylcholine was performed and compared with endothelium-independent relaxation Re sults. Pancreatic transplantation normalized the increases in glucose and total glycosylated hemoglobin levels and the decrease in serum ins ulin levels. Diabetes resulted in impaired relaxation to acetylcholine without altering relaxation to nitroglycerin. Pancreatic transplantat ion completely restored the defective relaxation to acetylcholine with out altering the relaxation to nitroglycerin. Conclusions. These resul ts suggest that pancreatic transplantation selectively improved endoth elium-dependent relaxation as opposed to a generalized improvement in vascular smooth muscle reactivity. Furthermore, these studies suggest for the first time that one aspect of vascular complications (i.e., en dothelial dysfunction) is amenable to this surgical intervention.