Prevention of incipient diabetic cardiomyopathy by high-dose thiamine

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• Diabetic cardiomyopathy can progress toward overt heart failure with increased mortality. The hexosamine biosynthesis pathway has been implicated in signaling for fibrosis by the kidney. Thiamine (vitamin B_1) is an indispensable coenzyme and required at intracellular glucose metabolism. In this study, we assessed if decrease of flux through the hexosamine biosynthesis pathway induced by high-dose thiamine therapy counteracts diabetes-induced cardiac fibrosis. The diabetes model used was the streptozotocin-induced diabetic rat. Normal control and diabetic rats were studied for 2 weeks with and without thiamine, and followings were analyzed; plasma biochemicals (total cholesterol and triglycerides), morphological changes, mRNA abundance relevant to cardiac failure (brain natriuretic peptide) and fibrosis (transforming growth factor-β1, thrombospondine, fibronectin, plasminogen activator-I and connective tissue growth factor) as well as and matrix metalloproteinase activity were investigated. Thiamine repletion prevented diabetes-induced cardiac fibrosis without changes in plasma glucose concentration. This was achieved by prevention of thiamine depletion, increased pro-fibrotic mRNA abundance and decreased metalloproteinase activity in the heart of diabetic rats. O-glycosylated protein was significantly higher in the left ventricular of diabetic rats compared to control rats, which was decreased by thiamine administration. Thiamine repletion prevented diabetes-induced cardiac fibrosis in experimental diabetes, probably by suppression of hexosamine biosynthesis pathway.

• 日本トキシコロジー学会の論文
• 2008-10-01

著者

• Kitaura Y

  Third Department Of Internal Medicine Osaka Medical College

• Okajima Kiyotaka

  Department Of Internal Medicine Iii Osaka Medical College

• Otsuka Koji

  大阪医科大学 第三内科

• Otsuka Koji

  The Third Division Department Of Internal Medicine Osaka Medical College

• Kitaura Y

  Third Department Of Medicine Osaka Medical College

• Terasaki Fumio

  Third Department of Internal Medicine, Osaka Medical College

• Kono Tatsuji

  Third division of internal medicine, Osaka medical college

• Terasaki F

  大阪医科大学 第三内科

• Terasaki Fumio

  大阪薬科大学 薬物治療学研究室

• Terasaki Fumio

  大阪薬科大学 薬物治療学

• Kitaura Yasushi

  Department Of Cardiovascular Science And Medicine Chiba University Graduate School Of Medicine

• Otsuka Kaoru

  Third Division, Department of Internal Medicine, Osaka Medical College

• Kita Yoshio

  大阪医科大学 第3内科

• Otsuka Kuniaki

  Department Of Internal Medicine Iii Osaka Medical College

• Kawakami Yoshihide

  Third Division Department Of Internal Medicine Osaka Medical College

• Kawakami Yoshihide

  大阪医科大学 第3内科

• Kitaura Yasushi

  Third Department Of Internal Medicine Osaka Medical College

• Kitaura Yasushi

  Department Of Internal Medicine Iii Osaka Medical College

• Yamashita Kentaro

  Cardiovascular Center Nagoya Daini Red Cross Hospital

• Kohno Tatsuji

  Department Of Medicine Tokyo Women's Medical University Medical Center East

• Kono Tatsuji

  Third Division Of Internal Medicine Osaka Medical College

• Kohno Tatsuji

  Third Department Of Internal Medicine Osaka Medical College

• Kanzaki Yumiko

  Third Department Of Internal Medicine Osaka Medical College

• Otsuka Kuniaki

  Department Of Medicine Medical Center East Tokyo Women's Medical University

• Otsuka Kuniaki

  Department Of Internal Medicine Tokyo Women's Medical University Medical Center East

• Terasaki Fumio

  Department Of Internal Medicine Iii Osaka Medical College

• Terasaki Fumio

  Third Department Of Internal Medicine Osaka Medical College

• Terasaki Fumio

  The Third Division Department Of Internal Medicine Osaka Medical College

• Yoshida Kentaro

  Department Of Internal Medicine University Of Tsukuba

• Kihara Yasuki

  Division Of Cardiology Kobe General Hospital

• KOHDA Yuka

  Laboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences

• Kohda Yuka

  Laboratory Of Pharmacology Osaka University Of Pharmaceutical Sciences

• Shirakawa Hisashi

  Laboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences

• Yamane Kazuhiko

  Laboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences

• Tanaka Takao

  Laboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences

• Yoshida Kentaro

  Depatment Of Pediatrics Institute Of Clinical Medicine University Of Tsukuba

• Kita Yoshio

  Third Department Of Internal Medicine Osaka Medical College

• Yoshida Kentaro

  Department Of Cardiology Institute Of Clinical Medicine University Of Tsukuba

• Kono Tatsuji

  Third Division Department Of Internal Medicine Osaka Medical College

• Shirakawa Hisashi

  Laboratory Of Pharmacotherapy Osaka University Of Pharmaceutical Sciences

• Otsuka Kaoru

  Third Div. Dep. Of Internal Medicine Osaka Medical Coll.

• Terasaki Fumio

  Third Division Department Of Internal Medicine Osaka Medical College

• Yamane Kazuhiko

  Laboratory Of Pharmacotherapy Osaka University Of Pharmaceutical Sciences

• Kitaura Yasushi

  Laboratory Of Pharmacotherapy Osaka University Of Pharmaceutical Sciences

• Kitaura Yasushi

  Division Of Cardiology Department Of Internal Medicine Fujita Health University School Of Medicine

• TANAKA Takao

  Organization of Medical Education, Osaka Medical College

• Terasaki. Fumio

  The Third Division Department Of Internal Medicine Osaka Medical College

• Otsuka Koji

  Third Division Department Of Internal Medicine Osaka Medical College

• Kohda Yuka

  大阪薬科大学 薬物治療学研究室

• Tanaka Takao

  Laboratory Of Pharmacotherapy Osaka University Of Pharmaceutical Sciences

• Kohda Yukinao

  Department Of Cardiology University Of Tsukuba Graduate School Of Comprehensive Human Sciences

• Kohda Yuka

  Laboratory Of Pharmacotherapy Osaka University Of Pharmaceutical Sciences

• Tanaka Takao

  Organization Of Medical Education Osaka Medical College

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