Monogenic Diabetes and Integrated Stress Response Genes Display Altered Gene Expression in Type 1 Diabetes.
Journal
Diabetes
ISSN: 1939-327X
Titre abrégé: Diabetes
Pays: United States
ID NLM: 0372763
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
15
02
2021
accepted:
16
05
2021
pubmed:
27
5
2021
medline:
22
9
2021
entrez:
26
5
2021
Statut:
ppublish
Résumé
Type 1 diabetes (T1D) has a multifactorial autoimmune etiology, involving environmental prompts and polygenic predisposition. We hypothesized that pancreata from individuals with and at risk for T1D would exhibit dysregulated expression of genes associated with monogenic forms of diabetes caused by nonredundant single-gene mutations. Using a "monogenetic transcriptomic strategy," we measured the expression of these genes in human T1D, autoantibody-positive (autoantibody+), and control pancreas tissues with real-time quantitative PCR in accordance with the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines. Gene and protein expression was visualized in situ with use of immunofluorescence, RNAscope, and confocal microscopy. Two dozen monogenic diabetes genes showed altered expression in human pancreata from individuals with T1D versus unaffected control subjects. Six of these genes also saw dysregulation in pancreata from autoantibody+ individuals at increased risk for T1D. As a subset of these genes are related to cellular stress responses, we measured integrated stress response (ISR) genes and identified 20 with altered expression in T1D pancreata, including three of the four eIF2α-dependent kinases. Equally intriguing, we observed significant repression of the three arms of the ISR in autoantibody+ pancreata. Collectively, these efforts suggest monogenic diabetes and ISR genes are dysregulated early in the T1D disease process and likely contribute to the disorder's pathogenesis.
Identifiants
pubmed: 34035041
pii: db21-0070
doi: 10.2337/db21-0070
pmc: PMC8385619
doi:
Substances chimiques
Autoantibodies
0
Banques de données
figshare
['10.2337/figshare.14612202']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1885-1897Subventions
Organisme : NIAID NIH HHS
ID : P01 AI042288
Pays : United States
Organisme : NIH HHS
ID : S10 OD020026
Pays : United States
Organisme : NIDDK NIH HHS
ID : UC4 DK108132
Pays : United States
Informations de copyright
© 2021 by the American Diabetes Association.
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