Department of Pediatrics, Washington University School of Medicine, St, Louis, MO, USA.
Cardiovasc Diabetol. 2012 Jun 8;11:63. doi: 10.1186/1475-2840-11-63.
The heart derives energy from a wide variety of substrates including fatty acids, carbohydrates, ketones, and amino acids. The healthy heart generates up to 30% of its ATP from glucose. Under conditions of cardiac injury or stress, the heart relies even more heavily on glucose as a source of fuel. Glucose is transported into the heart by members of the family of facilitative glucose transporters (GLUTs). While research examining the transport of glucose into the heart has primarily focused on the roles of the classical glucose transporters GLUT1 and GLUT4, little is known about the functions of more newly identified GLUT isoforms in the myocardium.
In this study the presence and relative RNA message abundance of each of the known GLUT isoforms was determined in left ventricular tissue from two commonly used inbred laboratory mouse strains (C57BL/6J and FVB/NJ) by quantitative real time PCR. Relative message abundance was also determined in GLUT4 null mice and in murine models of dilated and hypertrophic cardiomyopathy.
GLUT4, GLUT1, and GLUT8 were found to be the most abundant GLUT transcripts in the normal heart, while GLUT3, GLUT10, and GLUT12 are present at relatively lower levels. Assessment of relative GLUT expression in left ventricular myocardium from mice with dilated cardiomyopathy revealed increased expression of GLUT1 with reduced levels of GLUT4, GLUT8, and GLUT12. Compensatory increase in the expression of GLUT12 was observed in genetically altered mice lacking GLUT4.
Glucose transporter expression varies significantly among murine models of cardiac dysfunction and involves several of the class III GLUT isoforms. Understanding how these more newly identified GLUT isoforms contribute to regulating myocardial glucose transport will enhance our comprehension of the normal physiology and pathophysiology of the heart.
心脏从各种底物中获取能量,包括脂肪酸、碳水化合物、酮体和氨基酸。健康的心脏有高达 30%的 ATP 来自葡萄糖。在心脏损伤或应激的情况下,心脏更依赖葡萄糖作为燃料来源。葡萄糖通过家族成员易化葡萄糖转运体(GLUTs)进入心脏。虽然研究主要集中在经典葡萄糖转运体 GLUT1 和 GLUT4 对葡萄糖进入心脏的转运作用,但对于心肌中更多新发现的 GLUT 同工型的功能知之甚少。
在这项研究中,通过定量实时 PCR 确定了两种常用近交系实验室小鼠(C57BL/6J 和 FVB/NJ)左心室组织中每种已知 GLUT 同工型的存在和相对 RNA 丰度。还在 GLUT4 缺失小鼠和扩张型和肥厚型心肌病的小鼠模型中确定了相对 mRNA 丰度。
GLUT4、GLUT1 和 GLUT8 被发现是正常心脏中最丰富的 GLUT 转录本,而 GLUT3、GLUT10 和 GLUT12 的表达水平相对较低。在扩张型心肌病小鼠的左心室心肌中评估相对 GLUT 表达显示 GLUT1 的表达增加,而 GLUT4、GLUT8 和 GLUT12 的水平降低。在缺乏 GLUT4 的基因改变小鼠中观察到 GLUT12 的代偿性增加。
葡萄糖转运体的表达在几种 III 类 GLUT 同工型的心脏功能障碍小鼠模型中差异很大。了解这些新发现的 GLUT 同工型如何有助于调节心肌葡萄糖转运,将增强我们对心脏正常生理学和病理生理学的理解。