The Ubiquitous Glucose Transporter GLUT-1 Belongs to the Glucose-Regulated Protein Family of Stress-Inducible Proteins

• Published in: Proceedings of the National Academy of Sciences - PNAS 1991-03, Vol.88 (6), p.2525-2529
• Main Authors: Wertheimer, Efrat, Sasson, Shlomo, Cerasi, Erol, Ben-Neriah, Yinon
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Calcimycin - pharmacology; Calcium; Cell Line; Cell lines; Facilitative glucose transport proteins; Fibroblasts; Fundamental and applied biological sciences. Psychology; Gene expression; Gene expression regulation; Glucose - pharmacology; glucose transporter; Heat shock proteins; Heat-Shock Proteins - genetics; Hexoses; Kinetics; Messenger RNA; Molecular and cellular biology; Molecular genetics; Monosaccharide Transport Proteins - genetics; Muscles; Nucleic Acid Hybridization; RNA; RNA - genetics; RNA - isolation & purification; RNA, Messenger - drug effects; RNA, Messenger - genetics; Starvation; Tunicamycin - pharmacology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.88.6.2525

In mammals, glucose transport is mediated by five structurally related glucose transporters that show a characteristic cell-specific expression. However, the rat brain/HepG2/erythrocyte-type glucose transporter GLUT-1 is expressed at low levels in most cells. The reason for this coexpression is not clear. GLUT-1 is negatively regulated by glucose. Another family of proteins, glucose-regulated proteins (GRPs), is also ubiquitously expressed and stimulated by glucose deprivation and other cellular stresses. We therefore hypothesized that GLUT-1 may be a glucose-regulated stress protein. This was tested by subjecting L8myocytes and NIH 3T3 fibroblasts to glucose starvation or exposure to the calcium ionophore A23187, 2-mercaptoethanol, or tunicamycin, all known to increase GRP levels. The mRNA for GLUT-1 was augmented by 50-300% in a time-dependent manner, similarly to the changes in GRP-78 mRNA. Ex vivo incubation of rat soleus muscles induced a marked and concomitant rise in the mRNA levels of GLUT-1 and GRP-78. Finally, calcium ionophore A23187 and 2-mercaptoethanol induced a 2- to 3-fold increase in the levels of the GLUT-1 protein and hexose uptake. In all instances in which GRP-78 and GLUT-1 responded to stress, the transcription of the cell-specific muscle/adipocyte-type insulin-responsive glucose transporter (GLUT-4) did not change. Thus, despite the lack of structural similarity, GLUT-1 and GRP-78 expression is regulated similarly, whereas the regulation of GLUT-4, which is structurally related to GLUT-1, is different. We propose that GLUT-1 belongs to the GRP family of stress proteins and that its ubiquitous expression may serve a specific purpose during cellular stress.