PhD Scientific Days 2024

Budapest, 9-10 July 2024

Molecular Medicine I.

Analysis of the potential role of the GLUT1 transporter in type 2 diabetes

Author(s)

Anna Kulin1,2, Nóra Kucsma2, Balázs Bohár3, Botond Literáti-Nagy4, László Korányi4, Judit Cserepes5, Anikó Somogyi6, Balázs Sarkadi1,2, Edit Szabó2, György Várady1,2
1: Doctoral School of Molecular Medicine, Semmelweis University, 1085 Budapest, Hungary
2: Institute of Enzymology, Research Centre for Natural Sciences, 1117 Budapest, Hungary
3: Doctoral School of Biology, Eötvös Loránd University, 1117 Budapest, Hungary
4: Drug Research Center, 8230 Balatonfüred, Hungary
5: CellPharma Kft, 1119 Budapest, Hungary
6: 2nd Department of Internal Medicine, Semmelweis University, 1088 Budapest, Hungary

Text of the abstract

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)