Abstract
Oxidative stress induced by hyperglycemia is a key factor in the pathogenesis of diabetes complications. Glutaredoxin 1(Grx1) is a cytosolic redox protein that catalyzes GSH-dependent thiol redox reactions and reversible protein S-glutathionylation. In humans, Grx1 antigen has previously been detected in plasma; however, it has hitherto been unclear if plasma Grx1 is enzymatically active, which would indicate an extracellular function of the protein. Given that glucose overload damages cells through oxidative stress responses, we investigated whether postprandial hyperglycemia induces changes in extracellular Grx1 in patients with abnormal glucose tolerance and healthy subjects. Using a novel sensitive fluorescent substrate assay, we demonstrated that plasma Grx consists of active protein. Grx antigen, activity and total antioxidant capacity were significantly elevated in patients compared to healthy subjects. In response to oral glucose tolerance test, Grx activity and antioxidant capacity increased significantly in healthy volunteers, however, not to the high levels of the patients. In conclusion, these results indicate an extracellular function of plasma Grx in blood glucose metabolism. Thus, Grx may be a marker of increased oxidative stress during hyperglycemia in healthy subjects and may be a risk marker of progression toward diabetes onset.
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Abbreviations
- Grx1:
-
Glutaredoxin1
- GSH:
-
Reduced glutathione
- IFG:
-
Impaired fasting glucose
- IGT:
-
Impaired glucose tolerance
- NADPH:
-
Nicotinamide adenine dinucleotide phosphate
- NFκB:
-
Transcription factor nuclear factor kappa beta
- OGTT:
-
Oral glucose tolerance test
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Acknowledgments
We thank the staff at Vårdcentralen Söderdoktorn especially the head Eva-Carin Meurling for supplying clinical facilities, and Anna Harrysson for skillful service regarding patient sampling. This study was funded from the Swedish Medical Association and Swedish Cancer Association (JSU, AH), KA Wallenberg foundation and the Swedish Research Council (AH), Family Erling-Persson Foundation (NRE, KB).
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The authors have no conflict of interest to declare.
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Communicated by Guido Pozza.
Yatao Du, Huihui Zhang and Sergio Montano have contributed equally to this study.
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Du, Y., Zhang, H., Montano, S. et al. Plasma glutaredoxin activity in healthy subjects and patients with abnormal glucose levels or overt type 2 diabetes. Acta Diabetol 51, 225–232 (2014). https://doi.org/10.1007/s00592-013-0498-2
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DOI: https://doi.org/10.1007/s00592-013-0498-2