EFFECT OF PANCREAS TRANSPLANTATION AND IMMUNOSUPPRESSION ON PROINSULIN SECRETION

Insulin resistance and increased demand for insulin secretion occur af ter successful pancreas transplantation. To investigate the potential effects of immunosuppression and pancreas transplantation on fasting b eta-cell function, we studied fasting proinsulin and 32,33 split proin sulin secretion cross-sectionally and longitudinally in segmental panc reatic graft recipients (SPx, n = 18); in whole-pancreas graft recipie nts (WPx, n = 13); in nondiabetic kidney transplant recipients (Kx, n = 14) and in normal subjects (Ns, n = 14). Basal insulin secretion rat es were significantly increased in SPx 15.8 (1.7), WPx 24.4 (4.5) and Kx 22.1 (2.1) vs Ns 9.7 (1.6) pmol min(-1) l(-1), p < 0.05, mean (SEM) . Total proinsulin, intact proinsulin and 32,33 split proinsulin conce ntrations were significantly higher in all the transplanted groups tha n in normal subjects (p < 0.05), whereas the total proinsulin to C-pep tide ratio and the 32,33 split proinsulin ratio were higher in SPx tha n in WPx, Kx and Ns ( < 0.05). In the longitudinal study, beta-cell fu nction in terms of proinsulin secretion remained stable for 1 year. In conclusion, fasting glucose homeostasis in pancreas-kidney transplant recipients is obtained at the expense of increased proinsulin secreti on and increased insulin secretion rates, primarily induced by immunos uppression. In segmental pancreas graft recipients, increased fasting proinsulin and 32,33 split proinsulin relative to the number of beta-c ells transplanted indicate more stress on the residual beta-cell and t herefore higher secretory demand than in whole pancreas transplant rec ipients. (C) 1998 John Wiley & Sons, Ltd.