Endocrine Secretory Reserve and Proinsulin Processing in Recipients of Islet of Langerhans Versus Whole Pancreas Transplants

OBJECTIVE: β-Cells have demonstrated altered proinsulin processing after islet transplantation. We compare β-cell metabolic responses and proinsulin processing in pancreas and islet transplant recipients with respect to healthy control subjects. RESEARCH DESIGN AND METHODS: We studied 15 islet and 32 pancreas transplant recipients. Islet subjects were subdivided into insulin-requiring (IR-ISL, n = 6) and insulin-independent (II-ISL, n = 9) groups. Ten healthy subjects served as control subjects. Subjects were administered an intravenous arginine stimulation test, and insulin, C-peptide, total proinsulin, intact proinsulin, and proinsulin fragment levels were determined from serum samples. Acute insulin response (AIR) and proinsulin processing rates were calculated. RESULTS: We found that basal insulin and C-peptide levels were higher in the pancreas group than in all other groups. II-ISL patients had basal insulin and C-peptide levels similar to healthy control subjects. The IR-ISL group had significantly lower AIRs than all other groups. Basal processing rates were higher in the pancreas and II-ISL groups than in healthy control subjects and the IR-ISL group. After arginine stimulation, all groups had elevated processing rates, with the exception of the IR-ISL group. CONCLUSIONS: Our data suggest that II-ISL transplant recipients can maintain basal metabolic parameters similar to healthy control subjects at the cost of a higher rate of proinsulin processing. IR-ISL transplant recipients, on the other hand, demonstrate both lower insulin response and lower basal rates of proinsulin processing even after arginine stimulation.