Pancreatic graft procurement, preservation, and transplantation surgery may result in damage to and loss of the integrity of endocrine cells and consequently in leakage of cell products into the insular vascular capillaries. Thus, the amount of alpha-, beta-, and pancreatic polypeptide (PP) cell products released into the vascular space of the recipient immediately after graft reperfusion may reflect islet cell injury. To test this hypothesis, we assessed glucagon, PP, C-peptide, and insulin levels in a prospective study of 22 consecutive renal-pancreatic transplantations. Transplantation-related parameters were used to account for differences in hormone release. Five grafts were preserved using Euro-Collins preservation fluid and 17 grafts were preserved using University of Wisconsin solution (UW). The first sign of a reinstalled physiological axis was the decrease of the blood glucose concentration after a median duration of 40 min (range 5-90 min) and the association of the recipient's ambient blood glucose levels with insulin release between 25 and 180 min after reperfusion. The delay period before a fall in blood glucose was observed correlated with cold ischemia time (rs = 0.73, P < 0.001, n = 21). An immediate and marked increase in plasma levels of glucagon (from 180 +/- 18 to 585 +/- 99 ng/L, mean +/- SEM), PP (from 57 +/- 8 to 122 +/- 13 pmol/L), C-peptide (from < 0.06 +/- 0.02 to 5.43 +/- 0.63 nmol/L), and insulin (from 0.15 +/- 0.21 to 2.05 +/- 0.26 nmol/L) was observed. C-peptide release correlated with glucagon (r = 0.76, P < 0.001) and PP (r = 0.60, P < 0.01). The hormone release was compared with computed tomography scans that were performed in the immediate postoperative period in 15 UW-preserved allografts. The diameter of the pancreatic head was increased and ranged from 4.5 to 7.7 cm (mean 6.2 cm). Peroperative C-peptide release significantly correlated with morphological graft changes reflected by the pancreatic head diameter (r = 0.58, P = 0.02). In a stepwise multiple regression analysis, cold ischemia time was a significant factor for the release of PP (r2 = 0.18, P = 0.049) and C-peptide (r2 = 0.35, P = 0.004). We suggest that peroperative hormone release reflects endocrine tissue damage. Furthermore, cold ischemia time may jeopardize the pancreatic allograft after relatively short preservation times, even when UW is used.