Taurine rescues pancreatic β‐cell stress by stimulating α‐cell transdifferentiation

Dipak Sarnobat, R. Charlotte Moffett, Jinfang Ma, Peter R. Flatt, Neville H. McClenaghan, Andrei I. Tarasov

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Abstract

The semi-essential ubiquitous amino acid taurine has been shown to alleviate obesity and hyperglycemia in humans; however, the pathways underlying the antidiabetic actions have not been characterized. We explored the effect of chronic taurine exposure on cell biology of pancreatic islets, in degenerative type 1-like diabetes. The latter was modeled by small dose of streptozotocin (STZ) injection for 5 days in mice, followed by a 10-day administration of taurine (2% w/v, orally) in the drinking water. Taurine treatment opposed the detrimental changes in islet morphology and β-/α-cell ratio, induced by STZ diabetes, coincidentally with a significant 3.9 ± 0.7-fold enhancement of proliferation and 40 ± 5% reduction of apoptosis in β-cells. In line with these findings, the treatment counteracted an upregulation of antioxidant (Sod1, Sod2, Cat, Gpx1) and downregulation of islet expansion (Ngn3, Itgb1) genes induced by STZ, in a pancreatic β-cell line. At the same time, taurine enhanced the transdifferentiation of α-cells into β-cells by 2.3 ± 0.8-fold, echoed in strong non-metabolic elevation of cytosolic Ca levels in pancreatic α-cells. Our data suggest a bimodal effect of dietary taurine on islet β-cell biology, which combines the augmentation of α-/β-cell transdifferentiation with downregulation of apoptosis. The dualism of action, stemming presumably from the intra- and extracellular modality of the signal, is likely to explain the antidiabetic potential of taurine supplementation. [Abstract copyright: © 2023 The Authors. BioFactors published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.]
Original languageEnglish
Pages (from-to)646-662
Number of pages17
JournalBioFactors
Volume49
Issue number3
Early online date30 Jan 2023
DOIs
Publication statusPublished online - 30 Jan 2023

Bibliographical note

Funding Information:
These studies were supported in part by Young Investigator Award from Diabetes UK to RCM and Ulster University strategic funding and award of a Vice‐Chancellor Research Studentship to DS. The authors thank Professor Frank Reimann, University of Cambridge, for the donation of breeding pairs of Glu; ROSA26‐eYFP mice from which the present colony of mice was derived. CreERT2

Publisher Copyright:
© 2023 The Authors. BioFactors published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.

Keywords

  • RESEARCH ARTICLE
  • RESEARCH ARTICLES
  • apoptosis
  • Ca2+ dynamics
  • taurine
  • type 1 diabetes
  • α/β‐cell transdifferentiation
  • Ca dynamics
  • α/β-cell transdifferentiation

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