INSULIN-SECRETION, INSULIN ACTION AND NON-INSULIN-DEPENDENT GLUCOSE-UPTAKE IN PANCREAS TRANSPLANT RECIPIENTS

To assess individual, factors responsible of overall glucose tolerance after successful pancreas transplantation, an iv glucose tolerance te st, with frequent blood sampling and tolbutamide administration to eli cit a second insulin response was used to estimate insulin sensitivity (S-I) and glucose effectiveness (S-G) With Bergman's minimal model. I nsulin secretion was calculated from the combined insulin-C-peptide ki netics method. These parameters were quantified in identically immunos uppressed transplants: ISPx, four segmental pancreas recipients with i mpaired glucose tolerance; TSPx, five segmental pancreas recipients wi th normal glucose tolerance; WPx, five whole pancreas recipients with normal glucose tolerance; and in two controls groups, Kx, eight nondia betic kidney recipients, and Ns, eight normal subjects. All participan ts had normal fasting plasma glucose and normal glycosylated hemoglobi n A(1C) levels. The glucose tolerance K-G value was significantly redu ced only in ISPx compared with Ns (P < 0.05). S-I was reduced by 60% i n ISPx, WPx, and Kx compared with normal subjects (P < 0.05), whereas S-I was reduced by 30% in TSPx compared with normal controls (P = NS). The reduction in S-G was the same in all pancreas transplanted groups , as compared to Kx and Ns (by 33% and 40%, respectively, P < 0.05). T he first-phase insulin secretion (0-5 min) was markedly reduced in ISP x and TSPx compared with Ns (by 76% and 50%), to Kx (by 84% and 66%) a nd to WPx (by 73% and 45%), respectively (P < 0.05), but similar to Ns in WPx. The overall incremental insulin secretion was reduced in ISPx compared with Ns, WPx, and Kx (by 38%, 62%, and 73%, respectively, P < 0.05) and reduced in TSPx compared to WPx and Kx (by 47% and 67%, re spectively, P < 0.05). Ns secreted 43% of the total amount of insulin during the first phase the corresponding Value was only 13% in ISPx us 24% in TSPx, 24% in Kx, and 25% in WPx, respectively (P < 0.05). In c onclusion, after pancreas transplantation, the overall glucose toleran ce is determined by the net effect of reductions in insulin sensitivit y and glucose effectiveness and in the adaptability of the beta-cells to ensure sufficient insulin secretion. beta-cell function was impaire d in both the whole pancreas and segmental transplant recipients, and the failure to increase insulin secretion sufficiently leads to glucos e intolerance.