10.5061/DRYAD.D7WM37Q4B
Josefsen, Knud
0000-0002-5093-2901
Rigshospitalet
Buschard, Karsten
Rigshospitalet
Tekin, Hasim
Rigshospitalet
Krogvold, Lars
Oslo University Hospital
Gerling, Ivan
University of Tennessee Health Science Center
Poicot, Flemming
Steno Diabetes Center
PDE12 expression data from diabetes patients and controls
Dryad
dataset
2022
FOS: Medical and health sciences
Axius Foundation*
Bagger Sørensen Foundation*
2022-10-06T00:00:00Z
2022-10-06T00:00:00Z
en
10187 bytes
4
CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
Type 1 diabetes (T1D) incidence is increased after COVID-19 infection in
children under 18 years of age. Interferon-α-activated oligoadenylate
synthetase and downstream RNAseL activation degrade pathogen RNA, but can
also damage host RNA when RNAseL activity is poorly regulated. One such
regulator is PDE12 which degrades 2′-5′ oligoadenylate units, thereby
decreasing RNAseL activity. We analyzed PDE12 expression in islets from
non-diabetic donors, individuals with newly (median disease duration 35
days) and recently (5 years) diagnosed T1D, and individuals with type 2
diabetes (T2D). We also analyzed PDE12 single-nucleotide polymorphisms
(SNPs) relative to T1D incidence. PDE12 expression was decreased in
individuals with recently diagnosed T1D, in three of five individuals with
newly diagnosed T1D, but not in individuals with T2D. Two rare PDE12 SNPs
were found to have odds ratios of 1.80 and 1.74 for T1D development. We
discuss whether decreased PDE12 expression after COVID-19 infection might
be part of the up to 2.5-fold increase in T1D incidence.
Human tissue: Pancreatic tissue from donors was collected in the Diabetes
Virus Detection (DiViD) and Network for Pancreatic Organ Donors with
Diabetes (nPOD) studies, with informed consent obtained from all
participants. Briefly, DiViD donors with diabetes had a surgical resection
of the pancreatic tail, between three and nine weeks after their type 1
diabetes diagnosis, while nPOD material originates from cadaveric organ
donors. The procedures were approved by The Norwegian Government’s
Regional Ethics Committee (reference 2009/1907); nPOD donors with approval
by the University of Tennessee Health Science Center (UTHSC) local
Institutional Review Board [reference 10-00848-XM]). All experiments were
performed in accordance with relevant guidelines and regulations.
Microdissection of pancreatic islets: Acquired pancreatic samples were
laser microdissected as described previously. Briefly, frozen tissue
sections from nPOD and DiViD were microdissected with the Arcturus Pixcell
II laser capture microdissection system (Arcturus Bioscience, Mountain
View, CA, USA). Islets from 2-5 sections per donor were detected by
autofluorescence and pooled together, and afterwards subjected to RNA
extraction with the Arcturus PicoPure RNA Isolation Kit (Applied
Biosystems, Grand Island, NY, USA). RNA quality and quantity were
validated with the Bioanalyzer 2100 (Agilent Technologies, Santa Clara,
CA, USA), and samples underwent gene expression analysis with the
Affymetrix expression arrays (Thermo Fisher, Santa Clara, CA, USA) as
described previously.
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