Human cardiomyocytes express high level of Na+/glucose cotransporter 1 (SGLT1)
Human cardiomyocytes express high level of Na+/glucose cotransporter 1 (SGLT1)
复制标题
DOI：
10.1002/jcb.10631
复制
发表时间：
2003-10-01
影响因子：
4
通讯作者：
Demarest, KT
中科院分区：
文献类型：
--
作者：
Zhou, LB;Cryan, EV;Demarest, KT
我们用真实的时间PCR方法定量测定了钠依赖性葡萄糖协同转运蛋白I和2（SGLT 1和SGLT 2）在23种人体组织中的基因表达。正如预测的那样，我们的结果显示，相对于肾脏（3E + 4分子/μ g总RNA），小肠中SGLT 1的表达非常高（1.2E + 6分子/μ g总RNA）。令人惊讶的是，我们观察到SGLT 1在人心脏中的表达出乎意料地高（3.4E + 5个分子/μ g总RNA），比在肾组织中观察到的高约10倍。DNA测序证实PCR扩增片段确实是人SGLT 1基因。此外，使用地高辛（DIG）标记的对应于人SGLT 1 cDNA的反义cRNA探针进行的原位杂交研究证实，人心肌细胞表达SGLT 1 mRNA。相比之下，SGLT 2在人体组织中的表达似乎是普遍存在的，水平范围为6.7 E + 4分子/μ g总RNA（骨骼肌）至3.2 E + 6分子/μ g总RNA（肾脏），比相同组织中SGLT 1的表达水平高10-100倍。我们发现人心肌细胞表达高水平的SGLT 1 RNA，这表明SGLT 1可能在心脏葡萄糖转运中发挥功能性作用。由于目前正在开发几种SGLT抑制剂作为潜在的抗糖尿病药物，因此评估心脏中SGLT 1抑制的功能后果可能很重要。(C)2003 Wiley-Liss，Inc.
We have quantitatively measured gene expression for the sodium-dependent glucose cotransporters I and 2(SGLT1 and SGLT2) in 23 human tissues using the method of real time PCR. As predicted, our results revealed that the expression of SGLT1 was very high in the small intestine (1.2E + 6 molecules/mug total RNA) relative to that in the kidney (3E + 4 molecules/mug total RNA). Surprisingly, we observed that the expression of SGLT1 in human heart was unexpectedly high (3.4E + 5 molecules/mug total RNA), approximately 10-fold higher than that observed in kidney tissue. DNA sequencing confirmed that the PCR amplified fragment was indeed the human SGLT1 gene. Moreover, in situ hybridization studies using a digoxigenin (DIG)-labeled antisense cRNA probe corresponding to human SGLT1 cDNA confirm that human cardiomyocytes express SGLT1 mRNA. In contrast, the expression of SGLT2 in human tissues appears to be ubiquitous, with levels ranging from 6.7E + 4 molecules/mug total RNA (in skeletal muscle) to 3.2E + 6 molecules/mug total RNA (in kidney), levels 10-100-fold higher than the expression of SGLT1 in the same tissues. Our finding that human cardiomyocytes express high levels of SGLT1 RNA suggests that SGLT1 may have a functional role in cardiac glucose transport. Since several SGLT inhibitors are currently in development as potential anti-diabetic agents, it may be important to assess the functional consequences of inhibition of SGLT1 in the heart. (C) 2003 Wiley-Liss, Inc.