論文 - 詳細
| RRC ID | 35998 |
|---|---|
| 著者 | Kanamori H, Takemura G, Goto K, Tsujimoto A, Mikami A, Ogino A, Watanabe T, Morishita K, Okada H, Kawasaki M, Seishima M, Minatoguchi S. |
| タイトル | Autophagic adaptations in diabetic cardiomyopathy differ between type 1 and type 2 diabetes. |
| ジャーナル | Autophagy |
| Abstract |
Little is known about the association between autophagy and diabetic cardiomyopathy. Also unknown are possible distinguishing features of cardiac autophagy in type 1 and type 2 diabetes. In hearts from streptozotocin-induced type 1 diabetic mice, diastolic function was impaired, though autophagic activity was significantly increased, as evidenced by increases in microtubule-associated protein 1 light chain 3/LC3 and LC3-II/-I ratios, SQSTM1/p62 (sequestosome 1) and CTSD (cathepsin D), and by the abundance of autophagic vacuoles and lysosomes detected electron-microscopically. AMP-activated protein kinase (AMPK) was activated and ATP content was reduced in type 1 diabetic hearts. Treatment with chloroquine, an autophagy inhibitor, worsened cardiac performance in type 1 diabetes. In addition, hearts from db/db type 2 diabetic model mice exhibited poorer diastolic function than control hearts from db/+ mice. However, levels of LC3-II, SQSTM1 and phosphorylated MTOR (mechanistic target of rapamycin) were increased, but CTSD was decreased and very few lysosomes were detected ultrastructurally, despite the abundance of autophagic vacuoles. AMPK activity was suppressed and ATP content was reduced in type 2 diabetic hearts. These findings suggest the autophagic process is suppressed at the final digestion step in type 2 diabetic hearts. Resveratrol, an autophagy enhancer, mitigated diastolic dysfunction, while chloroquine had the opposite effects in type 2 diabetic hearts. Autophagy in the heart is enhanced in type 1 diabetes, but is suppressed in type 2 diabetes. This difference provides important insight into the pathophysiology of diabetic cardiomyopathy, which is essential for the development of new treatment strategies. |
| 巻・号 | 11(7) |
| ページ | 1146-60 |
| 公開日 | 2015-1-1 |
| DOI | 10.1080/15548627.2015.1051295 |
| PMID | 26042865 |
| PMC | PMC4590644 |
| MeSH | Animals Autophagy* Diabetes Mellitus, Type 1 / complications* Diabetes Mellitus, Type 1 / pathology* Diabetes Mellitus, Type 2 / complications* Diabetes Mellitus, Type 2 / pathology* Diabetic Cardiomyopathies / complications* Diabetic Cardiomyopathies / pathology* Energy Metabolism Green Fluorescent Proteins / metabolism Mice, Inbred C57BL Microtubule-Associated Proteins / metabolism Myocardium / pathology Myocytes, Cardiac / pathology Myocytes, Cardiac / ultrastructure Rats Vacuoles / metabolism Vacuoles / ultrastructure |
| IF | 9.77 |
| 引用数 | 80 |
| WOS 分野 | CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC00806 |