Cardiac substrate uptake and metabolism in obesity and type-2 diabetes: role of sarcolemmal substrate transporters.
Cardiac substrate uptake and metabolism in obesity and type-2 diabetes: role of sarcolemmal substrate transporters.
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DOI：
10.1007/s11010-005-9030-5
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发表时间：
2007-05
影响因子：
4.3
通讯作者：
Luiken, Joost J. F. P.
中科院分区：
文献类型：
--
作者：
Coort, Susan L. M.;Bonen, Arend;van der Vusse, Ger J.;Glatz, Jan F. C.;Luiken, Joost J. F. P.
心血管疾病是肥胖和2型糖尿病（T2 DM）的主要死亡原因。底物代谢的改变被认为与这些疾病中心功能障碍和胰岛素抵抗的发展有关。在生理环境下，心脏主要利用长链脂肪酸（LCFA）（60-70%），其余由碳水化合物覆盖，即，葡萄糖（20%）和乳酸（10%）。LCFA和葡萄糖的细胞摄取受特定转运蛋白的肌膜量调节，即，脂肪酸转位酶（FAT）/CD 36和GLUT 4。这些转运蛋白不仅存在于肌膜上，也存在于细胞内的储存室中。增加的工作负荷和激素胰岛素都诱导FAT/CD 36和GLUT 4易位到肌膜。在这篇综述中，最近的研究结果胰岛素和收缩信号通路参与底物的摄取和利用的心肌细胞在生理条件下进行了讨论。胰岛素抵抗及其向T2 DM进展过程中底物摄取和利用的改变的新见解表明底物转运蛋白的关键作用。在肥胖向T2 DM发展的过程中，发现心脏脂质稳态的改变先于葡萄糖稳态的改变。在T2 DM的早期阶段，FAT/CD 36重新定位至肌膜与三酰甘油（TAG）的心肌蓄积相关，最终导致胰岛素刺激的GLUT 4易位受损。这些新的见解可能会导致新的策略，预防肥胖和2型糖尿病的心功能不全和胰岛素抵抗的发展。
Cardiovascular disease is the primary cause of death in obesity and type-2 diabetes mellitus (T2DM). Alterations in substrate metabolism are believed to be involved in the development of both cardiac dysfunction and insulin resistance in these conditions. Under physiological circumstances the heart utilizes predominantly long-chain fatty acids (LCFAs) (60–70%), with the remainder covered by carbohydrates, i.e., glucose (20%) and lactate (10%). The cellular uptake of both LCFA and glucose is regulated by the sarcolemmal amount of specific transport proteins, i.e., fatty acid translocase (FAT)/CD36 and GLUT4, respectively. These transport proteins are not only present at the sarcolemma, but also in intracellular storage compartments. Both an increased workload and the hormone insulin induce translocation of FAT/CD36 and GLUT4 to the sarcolemma. In this review, recent findings on the insulin and contraction signalling pathways involved in substrate uptake and utilization by cardiac myocytes under physiological conditions are discussed. New insights in alterations in substrate uptake and utilization during insulin resistance and its progression towards T2DM suggest a pivotal role for substrate transporters. During the development of obesity towards T2DM alterations in cardiac lipid homeostasis were found to precede alterations in glucose homeostasis. In the early stages of T2DM, relocation of FAT/CD36 to the sarcolemma is associated with the myocardial accumulation of triacylglycerols (TAGs) eventually leading to an impaired insulin-stimulated GLUT4-translocation. These novel insights may result in new strategies for the prevention of development of cardiac dysfunction and insulin resistance in obesity and T2DM.
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影响因子：
16.2
作者：
Bertoni, AG;Tsai, A;Brancati, FL
通讯作者：
Brancati, FL
影响因子：
4.8
作者：
Christoffersen, C;Bollano, E;Nielsen, LB
通讯作者：
Nielsen, LB
影响因子：
4.1
作者：
Boone, AN;Rodrigues, B;Brownsey, RW
通讯作者：
Brownsey, RW
DOI：
10.1152/ajpendo.2000.279.5.e1104
发表时间：
2000-11-01
影响因子：
5.1
作者：
Belke, DD;Larsen, TS;Severson, DL
通讯作者：
Severson, DL
影响因子：
4.3
作者：
Bonen, A;Luiken, JJFP;Glatz, JFC
通讯作者：
Glatz, JFC