| Autor: |
Christophe Beauloye, S. Horman, Edith Renguet, Luc Bertrand, P. Morue, M. De Loof, Audrey Ginion, Louis Hue, Laurent Bultot |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Archives of Cardiovascular Diseases Supplements. 11:235 |
| ISSN: |
1878-6480 |
| DOI: |
10.1016/j.acvdsp.2019.02.118 |
| Popis: |
Introduction At rest, the heart favors fatty acids to produce its energy switching to glucose in response to insulin at postprandial state. Diabetic heart features metabolic adaptation defaults and is no longer able to switch, producing its energy exclusively through fatty acid oxidation. This metabolic inflexibility is a major factor of cardiac dysfunction. Observations made in high-fat diet mouse model lead to an increase in cardiac protein acetylation. We hypothesized that modulation of acetylation impacts the ability of the heart to uptake glucose with a special focus on tubulin. Objectives Microtubules playing a key role in GLUT4 translocation to the plasma membrane, we evaluated the impact of tubulin acetylation on cardiac glucose uptake. Methods The model is primary cultured rat cardiomyocytes. Acetylation levels and signaling pathways are evaluated by western blotting. The impact of long term incubation (20 h) with different pharmacological reducers of acetylation (garcinol 10 μM and anacardic acid 25 μM) on basal and insulin (3 nM, 30 min)-stimulated glucose uptake are measured following the detritiation rate of 2-3H-glucose. Tubacin, the inhibitor of tubulin deacetylase and an adenovirus overexpressing a non-acetylable form of tubulin are used to modulate tubulin acetylation. Results Insulin induces a 6-fold increase in glucose transport. Pharmacologically inhibiting global acetylation increases basal glucose transport similarly to insulin stimulation. By contrast, increasing specifically tubulin acetylation using tubacin inhibits 40% of basal and insulin-induced glucose transport. Accordingly, the overexpression of a dominant negative form and non-acetylable form of tubulin decreases endogenous tubulin acetylation while increasing basal glucose transport. Finally, targeting tubulin acetylation partially restores fatty acid-mediated inhibition of glucose transport. Conclusion There is a clear correlation between tubulin acetylation and glucose uptake level. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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