Exploratory study reveals far reaching systemic and cellular effects of verapamil treatment in subjects with type 1 diabetes.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
03 03 2022
03 03 2022
Historique:
received:
05
03
2021
accepted:
07
02
2022
entrez:
4
3
2022
pubmed:
5
3
2022
medline:
14
4
2022
Statut:
epublish
Résumé
Currently, no oral medications are available for type 1 diabetes (T1D). While our recent randomized placebo-controlled T1D trial revealed that oral verapamil had short-term beneficial effects, their duration and underlying mechanisms remained elusive. Now, our global T1D serum proteomics analysis identified chromogranin A (CHGA), a T1D-autoantigen, as the top protein altered by verapamil and as a potential therapeutic marker and revealed that verapamil normalizes serum CHGA levels and reverses T1D-induced elevations in circulating proinflammatory T-follicular-helper cell markers. RNA-sequencing further confirmed that verapamil regulates the thioredoxin system and promotes an anti-oxidative, anti-apoptotic and immunomodulatory gene expression profile in human islets. Moreover, continuous use of oral verapamil delayed T1D progression, promoted endogenous beta-cell function and lowered insulin requirements and serum CHGA levels for at least 2 years and these benefits were lost upon discontinuation. Thus, the current studies provide crucial mechanistic and clinical insight into the beneficial effects of verapamil in T1D.
Identifiants
pubmed: 35241690
doi: 10.1038/s41467-022-28826-3
pii: 10.1038/s41467-022-28826-3
pmc: PMC8894430
doi:
Substances chimiques
Immunologic Factors
0
Insulin
0
Verapamil
CJ0O37KU29
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1159Subventions
Organisme : NIDDK NIH HHS
ID : UC4 DK098085
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK122160
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK078752
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK120379
Pays : United States
Organisme : NIDDK NIH HHS
ID : DP3 DK110844
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK079626
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK098085
Pays : United States
Informations de copyright
© 2022. The Author(s).
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