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      Coenzyme Q10 suppresses apoptosis of mouse pancreatic β-cell line MIN6

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          Abstract

          Background

          In mitochondrial diabetes, apoptosis of β-cells caused by mitochondrial stress plays an important role in impaired insulin secretion. Several studies have reported that coenzyme Q10 (CoQ10) has therapeutic effects on mitochondrial diabetes, but no reports have examined the fundamental effectiveness or mechanism of CoQ10 in mitochondrial diabetes. We previously reported in a Japanese article that CoQ10 has protective effects on pancreatic β-cells against mitochondrial stress using mouse pancreatic β-cell line MIN6 and staurosporine (STS). Here, we report that CoQ10 protects MIN6 cells against apoptosis caused by STS and describe the more detailed apoptotic cascade.

          Methods

          Apoptosis of MIN6 cells was induced by 0.5 µM STS treatment for specific periods with or without 30 μM CoQ10. The apoptosis cascade in MIN6 cells was then investigated using WST-8 assays, annexin-V staining, western blotting, and DNA degradation analysis.

          Results

          Sixteen hours of 0.5 μM STS treatment led to 47% cell viability, but pretreatment with 30 μM CoQ10 resulted in significantly higher viability of 76% (P < 0.01). CoQ10 also prevented translocation of phosphatidylserine from the inner leaflet to the outer leaflet of the cell membrane. CoQ10 prevented cytochrome c release from mitochondria and activation of caspase-3.

          Conclusion

          We concluded that CoQ10 protects pancreatic β-cells through anti-apoptotic effects against STS treatment.

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          Most cited references11

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          Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes.

          Type 2 diabetes is characterized by impaired insulin secretion. Some but not all studies suggest that a decrease in beta-cell mass contributes to this. We examined pancreatic tissue from 124 autopsies: 91 obese cases (BMI >27 kg/m(2); 41 with type 2 diabetes, 15 with impaired fasting glucose [IFG], and 35 nondiabetic subjects) and 33 lean cases (BMI <25 kg/m(2); 16 type 2 diabetic and 17 nondiabetic subjects). We measured relative beta-cell volume, frequency of beta-cell apoptosis and replication, and new islet formation from exocrine ducts (neogenesis). Relative beta-cell volume was increased in obese versus lean nondiabetic cases (P = 0.05) through the mechanism of increased neogenesis (P < 0.05). Obese humans with IFG and type 2 diabetes had a 40% (P < 0.05) and 63% (P < 0.01) deficit and lean cases of type 2 diabetes had a 41% deficit (P < 0.05) in relative beta-cell volume compared with nondiabetic obese and lean cases, respectively. The frequency of beta-cell replication was very low in all cases and no different among groups. Neogenesis, while increased with obesity, was comparable in obese type 2 diabetic, IFG, or nondiabetic subjects and in lean type 2 diabetic or nondiabetic subjects. However, the frequency of beta-cell apoptosis was increased 10-fold in lean and 3-fold in obese cases of type 2 diabetes compared with their respective nondiabetic control group (P < 0.05). We conclude that beta-cell mass is decreased in type 2 diabetes and that the mechanism underlying this is increased beta-cell apoptosis. Since the major defect leading to a decrease in beta-cell mass in type 2 diabetes is increased apoptosis, while new islet formation and beta-cell replication are normal, therapeutic approaches designed to arrest apoptosis could be a significant new development in the management of type 2 diabetes, because this approach might actually reverse the disease to a degree rather than just palliate glycemia.
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            Ubiquinol-10 is an effective lipid-soluble antioxidant at physiological concentrations.

            It is well known that ubiquinone-10 (coenzyme Q10, ubiquinone 50) acts as an electron carrier of the respiratory chain in mitochondria. In this paper we show that ubiquinol-10, the reduced form of ubiquinone-10, also efficiently scavenges free radicals generated chemically within liposomal membranes. Ubiquinol-10 is about as effective in preventing peroxidative damage to lipids as alpha-tocopherol, which is considered the best lipid-soluble antioxidant in humans. The number of radicals scavenged by each molecule of ubiquinol-10 is 1.1 under our experimental conditions. In contrast to alpha-tocopherol, ubiquinol-10 is not recycled by ascorbate. However, it is known that ubiquinol-10 can be recycled by electron transport carriers present in various biomembranes and possibly by some enzymes. We also show that ubiquinol-10 spares alpha-tocopherol when both antioxidants are present in the same liposomal membranes and that ubiquinol-10, like alpha-tocopherol, does not interact with reduced glutathione. Our data together with previous work on the antioxidant function of ubiquinol reported in the literature strongly suggest that ubiquinol-10 is an important physiological lipid-soluble antioxidant.
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              Maternally transmitted diabetes and deafness associated with a 10.4 kb mitochondrial DNA deletion.

              Diabetes mellitus (DM) is one of the most common chronic disorders of children and adults. Several reports have suggested an increased incidence of maternal transmission in some forms of DM. Therefore, we tested a pedigree with maternally transmitted DM and deafness for mitochondrial DNA mutations and discovered a 10.4 kilobase (kb) mtDNA deletion. This deletion is unique because it is maternally inherited, removes the light strand origin (OL) of mtDNA replication, inhibits mitochondrial protein synthesis, and is not associated with the hallmarks of mtDNA deletion syndromes. This discovery demonstrates that DM can be caused by mtDNA mutations and suggests that some of the heterogeneity of this disease results from the novel features of mtDNA genetics.
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                Author and article information

                Contributors
                +81-859-38-6517 , ohkura@grape.med.tottori-u.ac.jp
                Journal
                Diabetol Metab Syndr
                Diabetol Metab Syndr
                Diabetology & Metabolic Syndrome
                BioMed Central (London )
                1758-5996
                14 June 2018
                14 June 2018
                2018
                : 10
                : 47
                Affiliations
                [1 ]ISNI 0000 0001 0663 5064, GRID grid.265107.7, Division of Endocrinology and Metabolism, Molecular Medicine and Therapeutics, Faculty of Medicine, , Tottori University, ; 36-1 Nishi-chou, Yonago, Tottori 683-8504 Japan
                [2 ]ISNI 0000 0001 0663 5064, GRID grid.265107.7, Division of Cardiovascular Medicine, Endocrinology and Metabolism, Department of Molecular Medicine and Therapeutics, Faculty of Medicine, , Tottori University, ; Yonago, Tottori 683-8504 Japan
                [3 ]ISNI 0000 0001 0663 5064, GRID grid.265107.7, Division of Molecular Pharmacology, Faculty of Medicine, , Tottori University, ; Yonago, Tottori 683-8504 Japan
                [4 ]ISNI 0000 0001 0663 5064, GRID grid.265107.7, Department of Regional Medicine, Faculty of Medicine, , Tottori University, ; Yonago, Tottori 683-8504 Japan
                Article
                351
                10.1186/s13098-018-0351-4
                6000937
                29942356
                88a9fb4f-7f0c-4827-8763-0599608eee3e
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 12 April 2018
                : 5 June 2018
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Nutrition & Dietetics
                min6,coenzyme q10,staurosporine,apoptosis,mitochondrial diabetes
                Nutrition & Dietetics
                min6, coenzyme q10, staurosporine, apoptosis, mitochondrial diabetes

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