|
福島県立医科大学学術成果リポジトリ = Fukushima Medical University Repository >
A 医学部 = School of Medicine >
a10 学術雑誌論文等 = Journal Article >
このアイテムの引用には次の識別子を使用してください:
http://ir.fmu.ac.jp/dspace/handle/123456789/15
|
| タイトル: | Diacylglycerol kinase zeta inhibits myocardial atrophy and restores cardiac dysfunction in streptozotocin-induced diabetes mellitus |
| 著者: | Bilim, Olga
Takeishi, Yasuchika
Kitahara, Tatsuro
Arimoto, Takanori
Niizeki, Takeshi
Sasaki, Toshiki
Goto, Kaoru
Kubota, Isao |
| 学内所属: | 循環器・血液内科学講座 |
| 誌名/書名: | Cardiovascular Diabetology |
| 巻: | 4 |
| 開始ページ: | 2 |
| 発行日: | 2008年2月4日 |
| 抄録: | BACKGROUND: Activation of the diacylglycerol (DAG)-protein kinase C (PKC) pathway has been implicated in the pathogenesis of a number of diabetic complications. Diacylglycerol kinase (DGK) converts DAG to phosphatidic acid and acts as an endogenous regulator of PKC activity. Akt/PKB is associated with a downstream insulin signaling, and PKCbeta attenuates insulin-stimulated Akt phosphorylation. METHODS AND RESULTS: We examined transgenic mice with cardiac-specific overexpression of DGKzeta (DGKzeta-TG) compared to wild type (WT) mice in streptozotocin-induced (STZ, 150 mg/kg) diabetic and nondiabetic conditions. After 8 weeks, decreases in heart weight and heart weight/body weight ratio in diabetic WT mice were inhibited in DGKzeta-TG mice. Echocardiography at 8 weeks after STZ-injection demonstrated that decreases in left ventricular end-diastolic diameter and fractional shortening observed in WT mice were attenuated in DGKzeta-TG mice. Thinning of the interventricular septum and the posterior wall in diabetic WT hearts were blocked in DGKzeta-TG mice. Reduction of transverse diameter of cardiomyocytes isolated from the left ventricle in diabetic WT mice was attenuated in DGKzeta-TG mice. Cardiac fibrosis was much less in diabetic DGKzeta-TG than in diabetic WT mice. Western blots showed translocation of PKCbeta and delta isoforms to membrane fraction and decreased Akt/PKB phosphorylation in diabetic WT mouse hearts. However in diabetic DGKzeta-TG mice, neither translocation of PKC nor changes Akt/PKB phosphorylation was observed. CONCLUSION: DGKzeta modulates intracellular signaling and improves the course of diabetic cardiomyopathy. These data may suggest that DGKzeta is a new therapeutic target to prevent or reverse diabetic cardiomyopathy. |
| 出版者: | BioMed Central Ltd |
| 本文の言語: | eng |
| このページのURI: | http://ir.fmu.ac.jp/dspace/handle/123456789/15 |
| 本文URL: | http://ir.fmu.ac.jp/dspace/bitstream/123456789/15/1/1475-2840-7-2.pdf |
| ISSN: | 1475-2840 |
| DOI: | 10.1186/1475-2840-7-2 |
| PubMed番号: | 18241357 |
| 異版(出版者版等): | http://dx.doi.org/10.1186/1475-2840-7-2 |
| 権利情報: | © 2008 Bilim et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| 権利情報: | http://creativecommons.org/licenses/by/2.0 |
| 出現コレクション: | a10 学術雑誌論文等 = Journal Article
|
このリポジトリに保管されているアイテムは、他に指定されている場合を除き、著作権により保護されています。
|
