Exploratory study reveals far reaching systemic and cellular effects of verapamil treatment in subjects with type 1 diabetes
- PMID: 35241690
- PMCID: PMC8894430
- DOI: 10.1038/s41467-022-28826-3
Exploratory study reveals far reaching systemic and cellular effects of verapamil treatment in subjects with type 1 diabetes
Abstract
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.
© 2022. The Author(s).
Conflict of interest statement
The authors declare no competing interests.
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References
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- Palmer JP, et al. C-peptide is the appropriate outcome measure for type 1 diabetes clinical trials to preserve beta-cell function: Report of an ADA workshop, 21-22 October 2001. Diabetes. 2004;53:250–264. - PubMed
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