Hepatic Failure and Enhanced Oxidative Stress in Mitochondrial Diabetes

Endocrine Journal

Kiyomi NISHIMAKI⁷  Riko KITAZAWA²  Shigeo OHTA⁷  Takeshi KONDO²  Keiji IIDA¹  Hiroyuki YAMADA⁶  Yoshio FUJIOKA⁵  Hidesuke KAJI⁴  Kentaro TAKAHASHI¹  Sohei KITAZAWA²  Ryoko TAKENO¹  Masayo FUJIMOTO²  Yasuhiko OKIMURA³  Yutaka TAKAHASHI¹  Hidetsuna KITAMURA⁵  Kazuo CHIHARA¹  Genzo IGUCHI¹  Fumio KANDA¹ 

[1] Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine;Division of Pathology, Department of Pathology&Microbiology, Kobe University Graduate School of Medicine;Department of Basic Allied Medicine, Kobe University School of Medicine;College of Nursing Art and Culture;Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine;Division of Diabetes, Digestive, and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine;Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School

关键词: Mitochondria;    Mutation;    Diabetes;    Hepatic steatosis;    Oxidative stress;   

DOI  :  10.1507/endocrj.K07E-091

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(12)Cited-By(2)Mitochondrial diabetes is characterized by diabetes and hearing loss in maternal transmission with a heteroplasmic A3243G mutation in the mitochondrial gene. In patients with the mutation, it has been reported that hepatic involvement is rarely observed. We demonstrated a case of hypertrophic cardiomyopathy and hepatic failure with mitochondrial diabetes. To clarify the pathogenesis we analyzed the mitochondrial ultrastructure in the myocytes, the reactive oxygen species (ROS) production in the liver and the status of heteroplasmy of the mitochondrial A3243G mutation in the organs involved. In cardiomyocytes and skeletal muscle, electron microscopic analysis demonstrated typical morphological mitochondrial abnormalities. Immunohistochemical analysis demonstrated enhanced ROS production associated with marked steatosis in the liver, which is often associated with mitochondrial dysfunction. Analysis of the A3243G mutation revealed a substantial ratio of heteroplasmy in these organs including the liver. The presence of steatosis and enhanced oxidative stress in the liver suggested that hepatic failure was associated with mitochondrial dysfunction.

【 授权许可】

Unknown