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

Sergio J. Montano , Jacob Grünler , Deepika Nair , Michael Tekle , Aristi P. Fernandes , Xiang Hua , Arne Holmgren , Kerstin Brismar , Johanna S. Ungerstedt
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引用次数: 24

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.

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谷氨酰胺还蛋白介导的辅酶Q10治疗1型和2型糖尿病患者的氧化还原作用
补充辅酶Q10 (CoQ10)对糖尿病患者疾病进展和氧化状态的可能有益作用仍存在争议。在本研究中,1型和2型糖尿病患者口服辅酶q10, 100mg,每日两次,持续12周。我们评估了总抗氧化能力、氧化还原调节蛋白glutaredoxin 1 (Grx1)、CoQ10、氧化ldl -胆固醇、血脂和HbA1c的细胞内和细胞外水平。我们之前的研究表明,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活性以及与糖尿病类型无关的总抗氧化能力,表明改善了氧化程度较低的细胞外环境。对血清Grx1活性的影响在未接受他汀类药物治疗的患者中更为突出。相反,细胞内Grx1活性和mRNA水平的增加与他汀类药物治疗无关。氧化低密度脂蛋白胆固醇和脂质谱有显著改善,代谢控制(HbA1c)有改善的趋势。此外,我们首次描述了CoQ10是谷胱甘肽的直接底物,而Grx1催化了这一反应,从而提出了CoQ10还原的新机制,这可以解释我们发现的细胞内Grx1增加。总之,12周的辅酶q10治疗显著改善了细胞外氧化还原平衡和脂质谱,表明延长治疗可能对糖尿病的临床结果也有有益的影响。
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