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 journalArticle

13 Citations (Scopus)

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

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Pancreatectomy
Autologous Transplantation
Insulin
DNA
Cell Death
Chronic Pancreatitis
Genetic Markers
Hyperglycemia
Meals
Glucose

Keywords

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

Cite this

Unmethylated Insulin DNA Is Elevated After Total Pancreatectomy With Islet Autotransplantation : Assessment of a Novel Beta Cell Marker. / Bellin, M. D.; Clark, P.; Usmani-Brown, S.; Dunn, T. B.; Beilman, G. J.; Chinnakotla, S.; Pruett, T. L.; Ptacek, P.; Hering, B. J.; Wang, Z.; Gilmore, T.; Wilhelm, J. J.; Hodges, J. S.; Moran, A.; Herold, K. C.

In: American Journal of Transplantation, Vol. 17, No. 4, 01.04.2017, p. 1112-1118.

Research output: Contribution to journalArticle

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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.",
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