title: Glutaredoxin mediated redox effects of coenzyme Q10 treatment in type 1 and type 2 diabetes patients.
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.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sergio J
authors.initials: SJ
authors.lastname: Montano
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Jacob
authors.initials: J
authors.lastname: Grünler
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden; Hematology Center, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Deepika
authors.initials: D
authors.lastname: Nair
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Tekle
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Aristi P
authors.initials: AP
authors.lastname: Fernandes
authors.affiliation: Department of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Xiang
authors.initials: X
authors.lastname: Hua
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Arne
authors.initials: A
authors.lastname: Holmgren
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Brismar
authors.affiliation: Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden; Hematology Center, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Johanna S
authors.initials: JS
authors.lastname: Ungerstedt
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