Montano Sergio J, Grünler Jacob, Nair Deepika, Tekle Michael, Fernandes Aristi P, Hua Xiang, Holmgren Arne, Brismar Kerstin, Ungerstedt Johanna S
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden.
BBA Clin. 2015 Jun 10;4:14-20. doi: 10.1016/j.bbacli.2015.06.001. eCollection 2015 Dec.
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.
补充辅酶Q10（CoQ10）对糖尿病疾病进展和氧化状态的潜在有益作用仍存在争议。在本研究中，1型和2型糖尿病患者接受口服CoQ10治疗，每日两次，每次100毫克，持续12周。我们评估了总抗氧化能力、氧化还原调节蛋白谷氧还蛋白1（Grx1）的细胞内和细胞外水平、CoQ10、氧化型低密度脂蛋白胆固醇、血脂谱和糖化血红蛋白（HbA1c）。我们之前已经表明，与健康受试者相比，2型糖尿病患者的细胞外Grx1增加。在本研究中，CoQ10治疗显著降低了血清Grx1活性以及总抗氧化能力，且与糖尿病类型无关，这表明细胞外环境的氧化程度有所改善。在未接受他汀类药物治疗的患者中，对血清Grx1活性的影响更为显著。相反，细胞内Grx1活性以及mRNA水平在与他汀类药物治疗无关的情况下有所增加。氧化型低密度脂蛋白胆固醇和血脂谱有显著改善，代谢控制（HbA1c）有改善趋势。此外，我们首次描述CoQ10是谷胱甘肽的直接底物，且Grx1催化该反应，从而提出了一种CoQ10还原的新机制，这可以解释我们观察到的细胞内Grx1增加的现象。总之，12周的CoQ10治疗显著改善了细胞外氧化还原平衡和血脂谱，表明长期治疗可能对糖尿病的临床结局也有有益影响。
