title: Impaired proinsulin processing is a characteristic of transplanted islets.
abstract: We sought to determine whether recipients of islet transplants have defective proinsulin processing. Individuals who had islet allo- or autotransplantation were compared to healthy nondiabetic subjects. Insulin (I), total proinsulin (TP), intact proinsulin and C-peptide (CP) were measured in samples of fasting serum by immunoassay, and the ratios of TP/TP+I and TP/CP were calculated. Islet allotransplant recipients had elevated TP levels relative to nondiabetic controls (16.8 [5.5-28.8] vs. 8.4 [4.0-21.8] pmol/L; p < 0.05) and autologous transplant recipients (7.3 [0.3-82.3] pmol/L; p < 0.05). Islet autotransplant recipients had significantly higher TP/TP+I ratios relative to nondiabetic controls (35.9 +/- 6.4 vs. 13.9 +/- 1.4%; p < 0.001). Islet allotransplant recipients, some of whom were on insulin, tended to have higher TP/TP+I ratios. The TP/CP ratio was significantly higher in both islet autotransplant (8.9 [0.6-105.2]; p < 0.05) and allotransplant recipients (2.4 [0.8-8.8]; p < 0.001) relative to nondiabetic controls (1.4 [0.5-2.6]%). Consistent with these findings, TP/TP+I and TP/CP values in islet autotransplant recipients increased significantly by 1-year posttransplant compared to preoperative levels (TP/CP: 3.8 +/- 0.6 vs. 23.3 +/- 7.9%; p < 0.05). Both allo- and autotransplant subjects who received <10,000 IE/kg had higher TP/CP ratios than those who received >10,000 IE/kg. Islet transplant recipients exhibit defects in the processing of proinsulin similar to that observed in subjects with type 2 diabetes manifest as higher levels of total proinsulin and increased TP/TP+I and TP/CP ratios.
authors.affiliation: Department of Pathology and Laboratory Medicine, British Columbia Children's Hospital, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
authors.forename: A M
authors.initials: AM
authors.lastname: Klimek
authors.forename: G
authors.initials: G
authors.lastname: Soukhatcheva
authors.forename: D M
authors.initials: DM
authors.lastname: Thompson
authors.forename: G L
authors.initials: GL
authors.lastname: Warnock
authors.forename: M
authors.initials: M
authors.lastname: Salehi
authors.forename: H
authors.initials: H
authors.lastname: Rilo
authors.forename: D
authors.initials: D
authors.lastname: D'Alessio
authors.forename: G S
authors.initials: GS
authors.lastname: Meneilly
authors.forename: C
authors.initials: C
authors.lastname: Panagiotopoulos
authors.forename: C B
authors.initials: CB
authors.lastname: Verchere
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011384:Proinsulin / Q000378:metabolism*; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D011384:Proinsulin