Indirect and Direct Effects of SARS-CoV-2 on Human Pancreatic Islets.
Journal
Diabetes
ISSN: 1939-327X
Titre abrégé: Diabetes
Pays: United States
ID NLM: 0372763
Informations de publication
Date de publication:
01 07 2022
01 07 2022
Historique:
received:
15
10
2021
accepted:
04
04
2022
pubmed:
3
5
2022
medline:
29
6
2022
entrez:
2
5
2022
Statut:
ppublish
Résumé
Recent studies have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may induce metabolic distress, leading to hyperglycemia in patients affected by coronavirus disease 19 (COVID-19). We investigated the potential indirect and direct effects of SARS-CoV-2 on human pancreatic islets in 10 patients who became hyperglycemic after COVID-19. Although there was no evidence of peripheral anti-islet autoimmunity, the serum of these patients displayed toxicity on human pancreatic islets, which could be abrogated by the use of anti-interleukin-1β (IL-1β), anti-IL-6, and anti-tumor necrosis factor α, cytokines known to be highly upregulated during COVID-19. Interestingly, the receptors of those aforementioned cytokines were highly expressed on human pancreatic islets. An increase in peripheral unmethylated INS DNA, a marker of cell death, was evident in several patients with COVID-19. Pathology of the pancreas from deceased hyperglycemic patients who had COVID-19 revealed mild lymphocytic infiltration of pancreatic islets and pancreatic lymph nodes. Moreover, SARS-CoV-2-specific viral RNA, along with the presence of several immature insulin granules or proinsulin, was detected in postmortem pancreatic tissues, suggestive of β-cell-altered proinsulin processing, as well as β-cell degeneration and hyperstimulation. These data demonstrate that SARS-CoV-2 may negatively affect human pancreatic islet function and survival by creating inflammatory conditions, possibly with a direct tropism, which may in turn lead to metabolic abnormalities observed in patients with COVID-19.
Identifiants
pubmed: 35499468
pii: 146863
doi: 10.2337/db21-0926
pmc: PMC9490452
doi:
Substances chimiques
Cytokines
0
Proinsulin
9035-68-1
Banques de données
ClinicalTrials.gov
['NCT04463849']
figshare
['10.2337/figshare.19592836']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1579-1590Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK057846
Pays : United States
Organisme : NIAID NIH HHS
ID : K24 AI116925
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK045735
Pays : United States
Organisme : NIDDK NIH HHS
ID : R43 DK116577
Pays : United States
Informations de copyright
© 2022 by the American Diabetes Association.
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