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Cited by 103Pancreatic function and diabetesDiabetes and associated disordersTransplantation: Methods and Outcomes

Improvement in β-Cell Secretory Capacity After Human Islet Transplantation According to the CIT07 Protocol

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Rickels, Michael R., Liu, Chengyang, Shlansky-Goldberg, Richard D., Soleimanpour, Scott A., Vivek, Kumar, Kamoun, Malek, Min, Zaw, Markmann, Eileen +7 more·2013·Diabetes
DOI 10.2337/db12-1802PMC PMC3717864
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Abstract

The Clinical Islet Transplantation 07 (CIT07) protocol uses antithymocyte 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 after transplantation and compared those results with the results previously achieved by our group using the Edmonton protocol and normal subjects. All subjects were insulin free, with CIT07 subjects receiving fewer islet equivalents from a median of one donor compared with two donors for Edmonton protocol subjects. The acute insulin response to glucose-potentiated arginine (AIRpot) was greater in the CIT07 protocol than in the Edmonton protocol and was less in both cohorts than in normal subjects, with similar findings for C-peptide. The CIT07 subjects who completed reassessment at day 365 exhibited increasing AIRpot by trend relative to that of 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. Although several peritransplant differences may have each contributed to this improvement, the lack of deterioration in β-cell secretory capacity over time in the CIT07 protocol suggests that low-dose tacrolimus and sirolimus are not toxic to islets.

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  • The amount of islet mass that is lost immediately following transplantation has been reduced closer to 25%, and thus fewer islets have been needed to achieve insulin independence.

    “In particular, the amount of islet mass that is lost immediately following transplantation has been reduced closer to 25%, and thus fewer islets have been needed to achieve insulin independence.”

    From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [125]

    The Discussion reports improved functional islet mass with the CIT07 protocol and insulin independence achieved with fewer transplanted islets than under the historical Edmonton protocol. But the Abstract’s ∼25% figure refers to β-cell secretory capacity relative to normal in Edmonton-protocol recipients—not the percentage of islet mass lost immediately after transplantation. The paper does not quantify immediate loss under CIT07 as 25%. (LLM, conf=0.90)

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Authors
Rickels, M. R., Liu, C., Shlansky-Goldberg, R. D., Soleimanpour, S. A., Vivek, K., Kamoun, M., Min, Z., Markmann, E., Palangian, M., Dalton-Bakes, C., Fuller, C., Chiou, A. J., Barker, C. F., Luning Prak, E. T., & Naji, A.
Affiliations
  • University of Pennsylvania (US)
  • Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
Corresponding author
Rickels, Michael R.
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2013-07-17
Volume
62
Issue
8
Pages
2890-2897
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/db12-1802
PMC
PMC3717864
OpenAlex
W2151663279
Cited by
103
References
47
Citations by year
2026: 3 · 2025: 6 · 2024: 1 · 2023: 6 · 2022: 6 · 2021: 8 · 2020: 7 · 2019: 10 · 2018: 10 · 2017: 8 · 2016: 13 · 2015: 11 · 2014: 12 · 2013: 2
FWCI
12.50
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • National Institute of Diabetes and Digestive and Kidney Diseases (K08DK089117, U01DK070430, P30 DK 19525, P30DK020572, P30DK019525, T32DK007314)
  • National Center for Research Resources (UL1RR024134)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
Keywords
islet transplantation, Edmonton protocol, acute insulin response, islet engraftment, tacrolimus, rapamycin, immunosuppression, antithymocyte globulin, etanercept, C-peptide
MeSH terms
Insulin Secretion, Adult, C-Peptide, Diabetes Mellitus, Type 1, Female, Humans, Hypoglycemic Agents, Immunosuppressive Agents, Insulin, Male, Middle Aged, Islets of Langerhans Transplantation, Tacrolimus, Treatment Outcome, Sirolimus, Insulin-Secreting Cells

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