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Impaired Proinsulin Processing is a Characteristic of Transplanted Islets

  1. A. M. Klimek1,
  2. G. Soukhatcheva1,
  3. D. M. Thompson2,
  4. G. L. Warnock3,
  5. M. Salehi4,
  6. H. Rilo4,
  7. D. D’Alessio4,
  8. G. S. Meneilly2,
  9. C. Panagiotopoulos5,*,
  10. C. B. Verchere1,3,*

Article first published online: 20 AUG 2009

DOI: 10.1111/j.1600-6143.2009.02740.x

Issue

American Journal of Transplantation

American Journal of Transplantation

Volume 9, Issue 9, pages 2119–2125, September 2009

Additional Information

How to Cite

Klimek, A. M., Soukhatcheva, G., Thompson, D. M., Warnock, G. L., Salehi, M., Rilo, H., D’Alessio, D., Meneilly, G. S., Panagiotopoulos, C. and Verchere, C. B. (2009), Impaired Proinsulin Processing is a Characteristic of Transplanted Islets. American Journal of Transplantation, 9: 2119–2125. doi: 10.1111/j.1600-6143.2009.02740.x

Author Information

  1. 1

    Department of Pathology and Laboratory Medicine, British Columbia Children's Hospital, Child and Family Research Institute, University of British Columbia

  2. 2

    Department of Medicine

  3. 3

    Department of Surgery, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada

  4. 4

    Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Cincinnati, OH

  5. 5

    Department of Pediatrics, British Columbia Children's Hospital, Child & Family Research Institute, and University of British Columbia, Vancouver, British Columbia, Canada

* * Corresponding author: C. Bruce Verchere and Constadina Panagiotopoulos, verchere@interchange.ubc.ca, dpanagiotopoulos@cw.bc.ca

Publication History

  1. Issue published online: 20 AUG 2009
  2. Article first published online: 20 AUG 2009
  3. Received 27 February 2009, revised 24 April 2009 and accepted for publication 18 May 2009
Corrected by:

Erratum

Vol. 11, Issue 2, 414, Article first published online: 27 JAN 2011

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Keywords:

  • Autologous transplantation;
  • allograft function;
  • beta cell;
  • clinical islet transplantation;
  • islet transplantation;
  • insulin secretion

Islet allo- and auto-transplant recipients exhibit defects in proinsulin processing, manifest as elevated ratios of proinsulin/C-peptide, comparable to those observed in subjects with type 2 diabetes.

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.

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