Santalucía T, Camps M, Castelló A, Muñoz P, Nuel A, Testar X, Palacin M, Zorzano A
Departament de Bioquímica i Fisiologia, Facultat de Biologia, Universitat de Barcelona, Spain.
Endocrinology. 1992 Feb;130(2):837-46. doi: 10.1210/endo.130.2.1370797.
The expression of GLUT-1 (erythroid/Hep G2) and GLUT-4 (muscle/fat) glucose transporters was assessed during development in rat heart, skeletal muscle, and brown adipose tissue. GLUT-4 protein expression was detectable in fetal heart by day 21 of pregnancy; it increased progressively after birth, attaining levels close to those of adults at day 15 post natal. In contrast, GLUT-4 messenger RNA (mRNA) was already present in hearts from 17 day-old fetuses. GLUT-4 mRNA stayed low during early postnatal life in heart and brown adipose tissue and only increased after day 10 post natal. The expression pattern for GLUT-4 protein in skeletal muscle during development was comparable to that observed in heart. In contrast to heart and skeletal muscle, GLUT-4 protein in brown adipose tissue was detected in high levels (30% of adult) during late fetal life. During fetal life, GLUT-1 presented a very high expression level in brown adipose tissue, heart, and skeletal muscle. Soon after birth, GLUT-1 protein diminished progressively, attaining adult levels at day 10 in heart and skeletal muscle. GLUT-1 mRNA levels in heart followed a similar pattern to the GLUT-1 protein, being very high during fetal life and decreasing early in post natal life. GLUT-1 protein showed a complex pattern in brown adipose tissue: fetal levels were high, decreased after birth, and increased subsequently in post natal life, reaching a peak by day 9. Progesterone-induced postmaturity protected against the decrease in GLUT-1 protein associated with post natal life in skeletal muscle and brown adipose tissue. However, GLUT-4 induction was not blocked by postmaturity in any of the tissues subjected to study. These results indicate that: 1) during fetal and early post natal life, GLUT-1 is a predominant glucose transporter isotype expressed in heart, skeletal muscle, and brown adipose tissue; 2) during early post natal life there is a generalized GLUT-1 repression; 3) during development, there is a close correlation between protein and mRNA levels for GLUT-1, and therefore regulation at a pretranslational level plays a major regulatory role; 4) the onset of GLUT-4 protein induction occurs between days 20-21 of fetal life; based on data obtained in rat heart and brown adipose tissue, there is a dissociation during development between mRNA and protein levels for GLUT-4, suggesting modifications at translational or posttranslational steps; and 5) postmaturity blocks the decrease in GLUT-1 expression but not the induction of GLUT-4, observed soon after birth.(ABSTRACT TRUNCATED AT 400 WORDS)
在大鼠心脏、骨骼肌和棕色脂肪组织发育过程中，对葡萄糖转运蛋白GLUT-1（红细胞/肝癌细胞系Hep G2型）和GLUT-4（肌肉/脂肪型）的表达进行了评估。妊娠第21天时，在胎儿心脏中可检测到GLUT-4蛋白表达；出生后其表达逐渐增加，在出生后第15天达到接近成年大鼠的水平。相比之下，在妊娠17天的胎儿心脏中就已存在GLUT-4信使核糖核酸（mRNA）。在出生后的早期，心脏和棕色脂肪组织中的GLUT-4 mRNA水平较低，仅在出生后第10天之后才升高。发育过程中，骨骼肌中GLUT-4蛋白的表达模式与心脏中观察到的相似。与心脏和骨骼肌不同，在胎儿后期，棕色脂肪组织中的GLUT-4蛋白水平较高（为成年大鼠的30%）。在胎儿期，GLUT-1在棕色脂肪组织、心脏和骨骼肌中呈现出非常高的表达水平。出生后不久，GLUT-1蛋白逐渐减少，在心脏和骨骼肌中于出生后第10天达到成年水平。心脏中GLUT-1 mRNA水平与GLUT-1蛋白呈现相似模式，在胎儿期非常高，在出生后早期下降。GLUT-1蛋白在棕色脂肪组织中呈现复杂模式：胎儿期水平较高，出生后下降，随后在出生后阶段升高，在出生后第9天达到峰值。孕酮诱导的过期妊娠可防止骨骼肌和棕色脂肪组织中与出生后生活相关的GLUT-1蛋白减少。然而，在所研究的任何组织中，过期妊娠均未阻断GLUT-4的诱导。这些结果表明：1）在胎儿期和出生后早期，GLUT-1是心脏、骨骼肌和棕色脂肪组织中表达的主要葡萄糖转运蛋白同种型；2）在出生后早期存在普遍的GLUT-1抑制；3）在发育过程中，GLUT-1的蛋白和mRNA水平之间存在密切相关性，因此转录前水平的调节起主要调节作用；4）GLUT-4蛋白诱导的起始发生在胎儿期第20 - 21天之间；基于在大鼠心脏和棕色脂肪组织中获得的数据，发育过程中GLUT-4的mRNA和蛋白水平存在分离，提示在翻译或翻译后步骤存在修饰；5）过期妊娠可阻断出生后不久观察到的GLUT-1表达下降，但不影响GLUT-4的诱导。（摘要截选至400字）
