Tal M, Kahn B B, Lodish H F
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142.
Endocrinology. 1991 Oct;129(4):1933-41. doi: 10.1210/endo-129-4-1933.
In normal fed rats the low Km glucose transporter GLUT-1 is expressed only in one row of hepatocytes immediately surrounding a terminal hepatic venule, while the high Km GLUT-2 is expressed in every hepatocyte. Previously, we showed that additional perivenous hepatocytes express GLUT-1 in fasting animals. In diabetes, as in starvation, the liver functions to release glucose into the circulation, but unlike starvation, circulating extracellular glucose is high in diabetes. By immunofluorescence and Western blotting we studied whether glucose or insulin is the primary extracellular signal for inducing GLUT-1 expression in hepatocytes. We observed that streptozocin-induced diabetes causes induction of GLUT-1 expression in the plasma membrane of hepatocytes within four cell rows of a terminal hepatic venule; GLUT-2 expression is unaltered. Chronic insulin treatment of diabetic rats reduces the number of rows of hepatocytes expressing GLUT-1 from approximately four to approximately two. In contrast, chronic insulin infusion into nondiabetic rats does not affect the number of hepatocytes expressing GLUT-1. Thus, both fasting and diabetes induce GLUT-1 expression in specific hepatocytes that normally do not express this gene. This induction correlates with low insulin levels in the blood, and not with circulating glucose levels.
在正常进食的大鼠中，低亲和力葡萄糖转运蛋白GLUT-1仅在紧邻终末肝静脉的一排肝细胞中表达，而高亲和力的GLUT-2则在每个肝细胞中表达。此前，我们发现禁食动物中额外的肝静脉周围肝细胞会表达GLUT-1。在糖尿病状态下，如同饥饿时一样，肝脏的功能是将葡萄糖释放到循环中，但与饥饿不同的是，糖尿病时循环中的细胞外葡萄糖水平较高。通过免疫荧光和蛋白质印迹法，我们研究了葡萄糖或胰岛素是否是诱导肝细胞中GLUT-1表达的主要细胞外信号。我们观察到，链脲佐菌素诱导的糖尿病会导致在终末肝静脉周围四排细胞范围内的肝细胞质膜中GLUT-1表达增加；GLUT-2的表达未发生改变。对糖尿病大鼠进行慢性胰岛素治疗可使表达GLUT-1的肝细胞排数从大约四排减少到大约两排。相反，向非糖尿病大鼠中慢性输注胰岛素并不影响表达GLUT-1的肝细胞数量。因此，禁食和糖尿病都会在通常不表达该基因的特定肝细胞中诱导GLUT-1表达。这种诱导与血液中低胰岛素水平相关，而与循环葡萄糖水平无关。
