IMT504 protects beta cells against apoptosis and maintains beta cell identity, without modifying proliferation.
apoptosis
oligodeoxynucleotides
proliferation
transcription factors
β-Cells
Journal
Physiological reports
ISSN: 2051-817X
Titre abrégé: Physiol Rep
Pays: United States
ID NLM: 101607800
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
revised:
26
07
2023
received:
11
01
2023
accepted:
28
07
2023
medline:
14
8
2023
pubmed:
12
8
2023
entrez:
12
8
2023
Statut:
ppublish
Résumé
We have demonstrated that oligodeoxynucleotide IMT504 promotes significant improvement in the diabetic condition in diverse animal models. Based on these results, here we evaluated whether these effects observed in vivo could be due to direct effects on β-cells. We demonstrate by immunofluorescence that IMT504 enters the cell and locates in cytoplasm where it induces GSK-3β phosphorylation that inactivates this kinase. As GSK-3β tags Pdx1 for proteasomal degradation, by inactivating GSK-3β, IMT504 induces an increase in Pdx1 protein levels, demonstrated by Western blotting. Concomitantly, an increase in Ins2 and Pdx1 gene transcription was observed, with no significant increase in insulin content or secretion. Enhanced Pdx1 is promising since it is a key transcription factor for insulin synthesis and is also described as an essential factor for the maintenance β-cell phenotype and function. Dose-dependent inhibition of H
Identifiants
pubmed: 37568265
doi: 10.14814/phy2.15790
pmc: PMC10421975
doi:
Substances chimiques
IMT504
0
Glycogen Synthase Kinase 3 beta
EC 2.7.11.1
Oligodeoxyribonucleotides
0
Insulin
0
Cytokines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e15790Informations de copyright
© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.
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