Postnatal increase in insulin-sensitive glucose transporter expression is associated with improved recovery of postischemic myocardial function.
Postnatal increase in insulin-sensitive glucose transporter expression is associated with improved recovery of postischemic myocardial function.
复制标题
出生后胰岛素敏感葡萄糖转运蛋白表达的增加与缺血后心肌功能恢复的改善有关。
DOI：
10.1016/s0022-5223(03)00034-5
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
delNido,PedroJ
中科院分区：
文献类型：
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作者：
Friehs,Ingeborg;Cao-Danh,Hung;Stamm,Christof;Cowan,DouglasB;McGowan,FrancisX;delNido,PedroJ
目的：葡萄糖是心脏发育过程中产生能量的重要底物。缺血和再灌注期间葡萄糖摄取率和代谢的增加与缺血后心肌恢复密切相关。糖酵解的初始限速步骤是葡萄糖转运蛋白（GLUT-1和GLUT-4）将葡萄糖转运穿过质膜。我们假设，在发育中的心脏中GLUT-1和GLUT-4表达的变化导致葡萄糖摄取能力的年龄依赖性适应性变化，并影响缺血耐受性。方法：采用正交设计法采用免疫印迹法检测GLUT-1和GLUT-4在1、2、3周龄和成年兔心肌组织中的表达。以2-脱氧葡萄糖为底物，用~（31）P-核磁共振法测定离体灌流心脏葡萄糖摄取率。以Langendorff模式用晶体缓冲液或缓冲液加GLUT-4特异性抗体灌注来自同龄兔的心脏，以确定GLUT-4介导的心肌保护作用。心脏进行30分钟的常温缺血，然后再灌注。在缺血前和缺血后测量心脏收缩功能。组织乳酸盐的积累，在缺血结束时测量所有组的结论：胰岛素调节的葡萄糖转运蛋白（GLUT-4）的表达在心脏出生后逐渐增加，达到接近成人水平的3周龄。与较高量的GLUT-4蛋白相对应，在老年心脏中观察到缺血后收缩功能的恢复改善，这与无氧糖酵解能力增加有关。干预，以加速出生后GLUT-4的表达可能会提高缺血耐受性的新生儿心脏。
OBJECTIVE: Glucose is an important substrate for energy production in the developing heart. Increased glucose uptake rate and metabolism during ischemia and reperfusion are closely linked to postischemic myocardial recovery. The initial rate-limiting step for glycolysis is the transport of glucose across the plasma membrane by glucose transporters (GLUT-1 and GLUT-4). We hypothesized that changes in GLUT-1 and GLUT-4 expression in developing hearts lead to age-dependent adaptive changes in glucose uptake capacity and influence tolerance to ischemia. METHODS: Western-immunoblotting was performed to determine GLUT-1 and GLUT-4 expression in myocardial tissue from 1, 2, and 3-week-old and adult rabbits. Glucose uptake rate was measured with31P-nuclear magnetic resonance spectroscopy using 2-deoxyglucose as substrate in isolated perfused hearts. Hearts from same age rabbits were perfused in the Langendorff mode with crystalloid buffer or buffer plus a GLUT-4 specific antibody in order to determine GLUT-4 mediated effects on myocardial protection. The hearts were subjected to 30 minutes of normothermic ischemia followed by reperfusion. Cardiac contractile function measurements were obtained pre- and postischemia. Tissue lactate accumulation was measured in all groups at end-ischemia CONCLUSIONS: Insulin-regulated glucose transporter (GLUT-4) expression in the heart increased gradually after birth reaching nearly adult levels by 3 weeks of age. Corresponding with the higher amount of GLUT-4 protein, improved recovery of postischemic contractile function was seen in older hearts in association with increased anaerobic glycolytic capacity. Interventions to accelerate postnatal GLUT-4 expression may improve ischemic tolerance in the neonatal heart.