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Paracrine regulation and improvement of β-cell function by thioredoxin.
Redox Biol. 2020 07; 34:101570.RB

Abstract

The failure of insulin-producing β-cells is the underlying cause of hyperglycemia in diabetes mellitus. β-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 β-cell culture, isolated pancreatic islets, and pancreatic islet transplantation modelling low oxygen supply. Protein levels of cytosolic Trx1 and Trx reductase (TrxR) 1 significantly decreased, while mitochondrial Trx2 and TrxR2 increased upon hypoxia and reoxygenation. Interestingly, Trx1 was secreted by β-cells during hypoxia. Moreover, murine and human pancreatic islet grafts released Trx1 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 Trx1 on β-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 β-cells.

Authors+Show Affiliations

Institute for Medical Biochemistry and Molecular Biology, University Medicine, University of Greifswald, Germany; Department of Neurology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.Clinical Research Unit, Center of Internal Medicine, Justus-Liebig-University, Giessen, Germany. Electronic address: sebastian.petry@innere.med.uni-giessen.de.Institute for Medical Biochemistry and Molecular Biology, University Medicine, University of Greifswald, Germany.Clinical Research Unit, Center of Internal Medicine, Justus-Liebig-University, Giessen, Germany.Clinical Research Unit, Center of Internal Medicine, Justus-Liebig-University, Giessen, Germany.Institute for Medical Biochemistry and Molecular Biology, University Medicine, University of Greifswald, Germany. Electronic address: horst@lillig.de.Clinical Research Unit, Center of Internal Medicine, Justus-Liebig-University, Giessen, Germany. Electronic address: thomas.linn@innere.med.uni-giessen.de.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32473461

Citation

Hanschmann, Eva-Maria, et al. "Paracrine Regulation and Improvement of Β-cell Function By Thioredoxin." Redox Biology, vol. 34, 2020, p. 101570.
Hanschmann EM, Petry SF, Eitner S, et al. Paracrine regulation and improvement of β-cell function by thioredoxin. Redox Biol. 2020;34:101570.
Hanschmann, E. M., Petry, S. F., Eitner, S., Maresch, C. C., Lingwal, N., Lillig, C. H., & Linn, T. (2020). Paracrine regulation and improvement of β-cell function by thioredoxin. Redox Biology, 34, 101570. https://doi.org/10.1016/j.redox.2020.101570
Hanschmann EM, et al. Paracrine Regulation and Improvement of Β-cell Function By Thioredoxin. Redox Biol. 2020;34:101570. PubMed PMID: 32473461.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Paracrine regulation and improvement of β-cell function by thioredoxin. AU - Hanschmann,Eva-Maria, AU - Petry,Sebastian Friedrich, AU - Eitner,Susanne, AU - Maresch,Constanze Christin, AU - Lingwal,Neelam, AU - Lillig,Christopher Horst, AU - Linn,Thomas, Y1 - 2020/05/16/ PY - 2020/04/11/received PY - 2020/05/07/accepted PY - 2020/5/31/pubmed PY - 2020/5/31/medline PY - 2020/5/31/entrez SP - 101570 EP - 101570 JF - Redox biology JO - Redox Biol VL - 34 N2 - The failure of insulin-producing β-cells is the underlying cause of hyperglycemia in diabetes mellitus. β-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 β-cell culture, isolated pancreatic islets, and pancreatic islet transplantation modelling low oxygen supply. Protein levels of cytosolic Trx1 and Trx reductase (TrxR) 1 significantly decreased, while mitochondrial Trx2 and TrxR2 increased upon hypoxia and reoxygenation. Interestingly, Trx1 was secreted by β-cells during hypoxia. Moreover, murine and human pancreatic islet grafts released Trx1 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 Trx1 on β-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 β-cells. SN - 2213-2317 UR - https://www.unboundmedicine.com/medline/citation/32473461/Paracrine_regulation_and_improvement_of_β-cell_function_by_thioredoxin L2 - https://linkinghub.elsevier.com/retrieve/pii/S2213-2317(20)30568-1 DB - PRIME DP - Unbound Medicine ER -
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