Dehydro-Tocotrienol-β Counteracts Oxidative-Stress-Induced Diabetes Complications in <i>db/db</i> Mice
Gustav Dallner,
Magnus Bentinger,
Shafaat Hussain,
Indranil Sinha,
Jiangning Yang,
Cheng Schwank-Xu,
Xiaowei Zheng,
Ewa Swiezewska,
Kerstin Brismar,
Ismael Valladolid-Acebes,
Michael Tekle
Affiliations
Gustav Dallner
Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-17177 Stockholm, Sweden
Magnus Bentinger
Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-17177 Stockholm, Sweden
Shafaat Hussain
Department of Molecular and Clinical Medicine, University of Gothenburg, SE-41345 Gothenburg, Sweden
Indranil Sinha
Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, SE-17177 Stockholm, Sweden
Jiangning Yang
Department of Medicine, Division of Cardiology, Karolinska Institutet, SE-17177 Stockholm, Sweden
Cheng Schwank-Xu
Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-17177 Stockholm, Sweden
Xiaowei Zheng
Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-17177 Stockholm, Sweden
Ewa Swiezewska
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, PL-02-106 Warsaw, Poland
Kerstin Brismar
Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-17177 Stockholm, Sweden
Ismael Valladolid-Acebes
Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-17177 Stockholm, Sweden
Michael Tekle
Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-17177 Stockholm, Sweden
Hyperglycemia, hyperlipidemia, and adiposity are the main factors that cause inflammation in type 2 diabetes due to excessive ROS production, leading to late complications. To counteract the effects of increased free radical production, we searched for a compound with effective antioxidant properties that can induce coenzyme Q biosynthesis without affecting normal cellular functions. Tocotrienols are members of the vitamin E family, well-known as efficient antioxidants that are more effective than tocopherols. Deh-T3β is a modified form of the naturally occurring tocotrienol-β. The synthesis of this compound involves the sequential modification of geranylgeraniol. In this study, we investigated the effects of this compound in different experimental models of diabetes complications. Deh-T3β was found to possess multifaceted capacities. In addition to enhanced wound healing, deh-T3β improved kidney and liver functions, reduced liver steatosis, and improved heart recovery after ischemia and insulin sensitivity in adipose tissue in a mice model of type 2 diabetes. Deh-T3β exerts these positive effects in several organs of the diabetic mice without reducing the non-fasting blood glucose levels, suggesting that both its antioxidant properties and improvement in mitochondrial function are involved, which are central to reducing diabetes complications.
