Journalartikel

Jahr der Veröffentlichung: 2020

Zeitschrift: Redox Biology

Bandnummer: 34

ISSN: 2213-2317

Open Access Status: Gold

DOI Link: https://doi.org/10.1016/j.redox.2020.101570

Verlag: Elsevier

Abstract: 

The failure of insulin-producing beta-cells is the underlying cause of hyperglycemia in diabetes mellitus. beta-cell decay has been linked to hypoxia, chronic inflammation, and oxidative stress. Thioredoxin (Trx) proteins are major actors in redox signaling and essential for signal transduction and the cellular stress response. We have analyzed the cytosolic, mitochondrial, and extracellular Trx system proteins in hypoxic and cytokine-induced stress using beta-cell culture, isolated pancreatic islets, and pancreatic islet transplantation modelling low oxygen supply.

Protein levels of cytosolic Trxl and Trx reductase (TrxR) 1 significantly decreased, while mitochondrial Trx2 and TrxR2 increased upon hypoxia and reoxygenation. Interestingly, Trx1 was secreted by beta-cells during hypoxia. Moreover, murine and human pancreatic islet grafts released Trxl upon glucose stimulation. Survival of transplanted islets was substantially impaired by the TrxR inhibitor auranofin.

Since a release was prominent upon hypoxia, putative paracrine effects of Trxl on beta-cells were examined. In fact, exogenously added recombinant hTrx1 mitigated apoptosis and preserved glucose sensitivity in pancreatic islets subjected to hypoxia and inflammatory stimuli, dependent on its redox activity. Human subjects were studied, demonstrating a transient increase in extracellular Trx1 in serum after glucose challenge. This increase correlated with better pancreatic islet function. Moreover, hTrx1 inhibited the migration of primary murine macrophages.

In conclusion, our study offers evidence for paracrine functions of extracellular Trx1 that improve the survival and function of pancreatic beta-cells.

Harvard-Zitierstil: Hanschmann, E., Petry, S., Eitner, S., Maresch, C., Lingwal, N., Lillig, C., et al. (2020) Paracrine regulation and improvement of β-cell function by thioredoxin, Redox Biology, 34, Article 101570. https://doi.org/10.1016/j.redox.2020.101570

APA-Zitierstil: Hanschmann, E., Petry, S., Eitner, S., Maresch, C., Lingwal, N., Lillig, C., & Linn, T. (2020). Paracrine regulation and improvement of β-cell function by thioredoxin. Redox Biology. 34, Article 101570. https://doi.org/10.1016/j.redox.2020.101570