Unmethylated Insulin DNA Is Elevated After Total Pancreatectomy With Islet Autotransplantation: Assessment of a Novel Beta Cell Marker

M. D. Bellin, P. Clark, S. Usmani-Brown, T. B. Dunn, G. J. Beilman, S. Chinnakotla, T. L. Pruett, P. Ptacek, B. J. Hering, Z. Wang, T. Gilmore, J. J. Wilhelm, J. S. Hodges, A. Moran, K. C. Herold

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Beta cell death may occur both after islet isolation and during infusion back into recipients undergoing total pancreatectomy with islet autotransplantation (TPIAT) for chronic pancreatitis. We measured the novel beta cell death marker unmethylated insulin (INS) DNA in TPIAT recipients before and immediately after islet infusion (n = 21) and again 90 days after TPIAT, concurrent with metabolic functional assessments (n = 25). As expected, INS DNA decreased after pancreatectomy (p = 0.0002). All TPIAT recipients had an elevated unmethylated INS DNA ratio in the first hours following islet infusion. In four samples (three patients), INS DNA was also assessed immediately after islet isolation and again before islet infusion to assess the impact of the isolation process: Unmethylated and methylated INS DNA fractions both increased over this interval, suggesting death of beta cells and exocrine tissue before islet infusion. Higher glucose excursion with mixed-meal tolerance testing was associated with persistently elevated INS DNA at day 90. In conclusion, we observed universal early elevations in the beta cell death marker INS DNA after TPIAT, with pronounced elevations in the islet supernatant before infusion, likely reflecting beta cell death induced by islet isolation. Persistent posttransplant elevation of INS DNA predicted greater hyperglycemia at 90 days.

Original languageEnglish (US)
Pages (from-to)1112-1118
Number of pages7
JournalAmerican Journal of Transplantation
Volume17
Issue number4
DOIs
StatePublished - Apr 1 2017

Bibliographical note

Funding Information:
Research reported in this publication was supported in part by awards from the National Center for Advancing Translational Sciences (UL1TR000114), the National Institutes of Diabetes and Digestive and Kidney Diseases (R03-DK102469, PI Bellin; R01DK057846, R42DK095639, DP3DK101122, and UC4DK104205, PI Herold) and the Juvenile Diabetes Research Foundation (2014-142-S-B, PI Herold).

Publisher Copyright:
© Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons

Keywords

  • biomarker
  • cell death
  • clinical research/practice
  • diabetes: type 1
  • endocrinology/diabetology
  • islet isolation
  • islet transplantation
  • islets of Langerhans
  • translational research/science

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