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

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13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2119-2125
Number of pages7
JournalAmerican Journal of Transplantation
Volume9
Issue number9
DOIs
StatePublished - Sep 2009

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Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

Klimek, A. M., Soukhatcheva, G., Thompson, D. M., Warnock, G. L., Salehi, M., Rilo, H., D'Alessio, D., Meneilly, G. S., Panagiotopoulos, C., & Verchere, C. B. (2009). Impaired proinsulin processing is a characteristic of transplanted islets. American Journal of Transplantation, 9(9), 2119-2125. https://doi.org/10.1111/j.1600-6143.2009.02740.x