The Regulation of Insulin-Stimulated Cardiac Glucose Transport via Protein Acetylation.
The Regulation of Insulin-Stimulated Cardiac Glucose Transport via Protein Acetylation.
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DOI：
10.3389/fcvm.2018.00070
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发表时间：
2018
影响因子：
3.6
通讯作者：
Bertrand L
中科院分区：
文献类型：
--
作者：
Renguet E;Bultot L;Beauloye C;Horman S;Bertrand L
细胞催化剂是细胞从各种底物产生能量以维持其功能的能力。为了优化这种能量产生，细胞能够通过调节几种调节酶根据底物可用性在各种代谢途径之间切换。这种代谢灵活性对于健康的心脏至关重要，心脏是一个需要大量ATP来维持其收缩功能的器官。在2型糖尿病中，过量的非糖基化营养素如脂肪酸、支链氨基酸或酮体诱导心脏代谢紊乱。其特征在于优先使用这些替代底物而损害葡萄糖，这参与心肌细胞功能障碍和糖尿病心肌病的发展。在过去的几十年中，已经仔细研究了导致这种代谢不稳定性的分子机制。1963年，Randle证明了脂肪酸代谢产生的一些代谢物的积累能够变构抑制葡萄糖代谢的调节步骤，导致心脏优先使用脂肪酸。然而，该模型不能完全概括糖尿病患者的观察结果，需要更复杂的模型。从不同实验室收集的最新证据中出现了一个新的难题，表明非葡萄糖底物的代谢诱导蛋白质乙酰化水平的增加，这伴随着葡萄糖转运的扰动。本综述的目的是收集，在一个合成的模型，不同的证据表明，乙酰化的作用，抑制胰岛素刺激的葡萄糖摄取在心肌。
Cellular catabolism is the cell capacity to generate energy from various substrates to sustain its function. To optimize this energy production, cells are able to switch between various metabolic pathways in accordance to substrate availability via a modulation of several regulatory enzymes. This metabolic flexibility is essential for the healthy heart, an organ requiring large quantities of ATP to sustain its contractile function. In type 2 diabetes, excess of non-glucidic nutrients such as fatty acids, branched-chain amino-acids, or ketones bodies, induces cardiac metabolic inflexibility. It is characterized by a preferential use of these alternative substrates to the detriment of glucose, this participating in cardiomyocytes dysfunction and development of diabetic cardiomyopathy. Identification of the molecular mechanisms leading to this metabolic inflexibility have been scrutinized during last decades. In 1963, Randle demonstrated that accumulation of some metabolites from fatty acid metabolism are able to allosterically inhibit regulatory steps of glucose metabolism leading to a preferential use of fatty acids by the heart. Nevertheless, this model does not fully recapitulate observations made in diabetic patients, calling for a more complex model. A new piece of the puzzle emerges from recent evidences gathered from different laboratories showing that metabolism of the non-glucidic substrates induces an increase in acetylation levels of proteins which is concomitant to the perturbation of glucose transport. The purpose of the present review is to gather, in a synthetic model, the different evidences that demonstrate the role of acetylation in the inhibition of the insulin-stimulated glucose uptake in cardiac muscle.