Improvement in β-Cell Secretory Capacity Following Human Islet Transplantation According to the CIT07 Protocol
- Michael R. Rickels1,
- Chengyang Liu2,
- Richard D. Shlansky-Goldberg3,
- Scott A. Soleimanpour1,
- Kumar Vivek2,
- Malek Kamoun4,
- Zaw Min2,
- Eileen Markmann2,
- Maral Palangian2,
- Cornelia Dalton-Bakes1,
- Carissa Fuller1,
- Allen J. Chiou1,
- Clyde F. Barker2,
- Eline T. Luning Prak4 and
- Ali Naji2
- 1Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, the
- 2Department of Surgery, Division of Transplantation, the
- 3Department of Radiology, Division of Interventional Radiology, and the
- 4Department of Pathology & Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
- Corresponding author: Michael R. Rickels, E-mail:
The Clinical Islet Transplantation 07 (CIT07) protocol utilizes anti-thymocyte globulin and etanercept induction, islet culture, heparinization and intensive insulin therapy, with the same low-dose tacrolimus and sirolimus maintenance immunosuppression as in the Edmonton protocol. To determine whether CIT07 improves engrafted islet β-cell mass, our center measured β-cell secretory capacity from glucose-potentiated arginine tests at days 75 and 365 post-transplant, and compared the results to those previously achieved by our group with the Edmonton protocol, and to normal. All subjects were insulin-free with CIT07 subjects receiving fewer islet equivalents from a median 1 vs. 2 donors in Edmonton subjects. The acute insulin response to glucose-potentiated arginine (AIRpot) was greater in CIT07 than Edmonton and less in both cohorts than normal, with similar findings for C-peptide. The CIT07 subjects who completed reassessment at day 365 exhibited increasing AIRpot by trend relative to day 75. These data indicate that engrafted islet β-cell mass is markedly improved with the CIT07 protocol, especially given more frequent use of single islet donors. While several peri-transplant differences may have each contributed to this improvement, the lack of deterioration in β-cell secretory capacity over time in CIT07 suggests that low-dose tacrolimus and sirolimus are not toxic to islets.
- Received December 20, 2012.
- Accepted April 24, 2013.
- © 2013 by the American Diabetes Association.
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