Glutaredoxin mediated redox effects of coenzyme Q10 treatment in type 1 and type 2 diabetes patients

BBA Clin. 2015 Jun 10;4:14-20. doi: 10.1016/j.bbacli.2015.06.001. eCollection 2015 Dec.

Abstract

The possible beneficial effects of coenzyme Q10 (CoQ10) supplementation on disease progression and oxidant status in diabetes remains debated. In the present study, patients with type 1 and type 2 diabetes were treated with oral CoQ10, 100 mg twice daily for 12 weeks. We assessed total antioxidant capacity, intra- and extracellular levels of the redox regulating protein glutaredoxin 1 (Grx1), CoQ10, oxidized LDL-cholesterol, lipid profile and HbA1c. We have previously shown that extracellular Grx1 is increased in patients with type 2 diabetes compared to healthy subjects. In the present study, CoQ10 treatment significantly decreased serum Grx1 activity as well as total antioxidant capacity independent of type of diabetes, indicating an improvement to a less oxidized extracellular environment. The effect on serum Grx1 activity was more prominent in patients not on statin treatment. Conversely, intracellular Grx1 activity as well as mRNA levels increased independent of statin treatment. There was a significant improvement in oxidized LDL-cholesterol and lipid profile, with a tendency to improved metabolic control (HbA1c). Additionally, we describe for the first time that CoQ10 is a direct substrate for glutathione, and that Grx1 catalyzes this reaction, thus presenting a novel mechanism for CoQ10 reduction which could explain our findings of an increased intracellular Grx1. In conclusion, 12 weeks CoQ10 treatment significantly improved the extracellular redox balance and lipid profile, indicating that prolonged treatment may have beneficial effects also on clinical outcome in diabetes.

•CoQ10 decreases oxidative stress markers as extracellular Grx1 and oxidized LDL.•CoQ10 decreases plasma total and LDL-cholesterol in diabetes patients.•We describe a novel mechanism for in vivo CoQ10 reduction via GSH, catalyzed by Grx1.

Keywords: CoQ10, coenzyme Q10; Coenzyme Q10; DM, diabetes mellitus; Diabetes mellitus; GR, glutathione reductase; GSH, glutathione; Glutaredoxin; Grx1, glutaredoxin 1; Human; Kcat, catalytic rate constant; NADP, nicotinamide dinucleotide phosphate; PBMC, peripheral blood mononuclear cell; ROS; TAC, total antioxidant capacity.