Faculty Collaboration Database

Unmethylated Insulin DNA Is Elevated After Total Pancreatectomy With Islet Autotransplantation: Assessment of a Novel Beta Cell Marker. Am J Transplant 2017 Apr;17(4):1112-1118

Date

10/25/2016

Pubmed ID

27643615

Pubmed Central ID

PMC5357596

DOI

10.1111/ajt.14054

Scopus ID

2-s2.0-84997132374 (requires institutional sign-in at Scopus site)   35 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.

Author List

Bellin MD, Clark P, Usmani-Brown S, Dunn TB, Beilman GJ, Chinnakotla S, Pruett TL, Ptacek P, Hering BJ, Wang Z, Gilmore T, Wilhelm JJ, Hodges JS, Moran A, Herold KC

Author

Ty Blink Dunn MD Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Biomarkers
Child
DNA
DNA Methylation
Diabetes Mellitus, Type 1
Female
Graft Rejection
Graft Survival
Humans
Insulin
Insulin-Secreting Cells
Islets of Langerhans Transplantation
Male
Pancreatectomy
Pancreatitis, Chronic
Postoperative Complications
Prognosis
Prospective Studies
Risk Factors
Transplantation, Autologous
Young Adult