Molecular Medicine I.
Introduction: Type 2 diabetes mellitus (T2DM) is a complex metabolic disease and various membrane transporters affect its development, progression, or treatments. The GLUT1 membrane protein is a key glucose transporter in numerous cell types and the expression level of this protein has a role in several diseases, including cancer, Alzheimer’s disease and T2DM.
Aims: In this work my aim was to studying the genetic and regulatory background of the expression level of GLUT1 and to analyze its possible association with T2DM.
Methods: The expression level of GLUT1 was measured in red blood cells (RBCs) by flow cytometry, while the genetic background was analyzed by qPCR and luciferase assay.
Result: We found significant associations between RBC GLUT1 levels and four SNPs. In individuals with the minor alleles of rs841848, rs1385129, and rs11537641 had increased, while in those having the variant rs841847 had decreased erythrocyte GLUT1 levels. In the luciferase reporter studies performed in HEK-293T and HepG2 cells, a similar SNP-dependent modulation was observed in most cases. These associations were linked to potential regulatory factors, including reduced glucose or serum levels, hypoxic conditions, and alterations in transcription factor binding sites.
Conclusion: Our research on GLUT1 may contribute to a more detailed understanding of the genetic and regulatory background of GLUT1 expression and its potential role in associated diseases.
Funding:
EFOP-3.6.3-VEKOP-16-2017-00009, Semmelweis University;
NKFIH OTKA (K128011)