Impaired proinsulin processing is a characteristic of transplanted islets

A. M. Klimek, G. Soukhatcheva, D. M. Thompson, G. L. Warnock, M. Salehi, H. Rilo, D. D'Alessio, G. S. Meneilly, C. Panagiotopoulos, C. B. Verchere

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2119-2125
Number of pages7
JournalAmerican Journal of Transplantation
Issue number9
StatePublished - Sep 2009
Externally publishedYes


  • Allograft function
  • Autologous transplantation
  • Beta cell
  • Clinical islet transplantation
  • Insulin secretion
  • Islet transplantation

ASJC Scopus subject areas

  • Transplantation
  • Pharmacology (medical)
  • Immunology and Allergy


Dive into the research topics of 'Impaired proinsulin processing is a characteristic of transplanted islets'. Together they form a unique fingerprint.

Cite this