Kocaeli, A. A.Tekin, C.Erçelik, M.Tezcan, G.Aksoy, S. A.Kocaeli, H.Bekar, A.Taşkapılıoğlu, M. O.Tolunay, S.Tunca, B.2024-12-032024-12-032023-01-011128-3602https://hdl.handle.net/11452/48809OBJECTIVE: Diabetes mellitus (DM)-mediated impaired glucose metabolism in-crease in the glioblastoma (GB) risk by inducing hyperglycemia and hyperinsulinemia. An inte-gral membrane transport protein, glucose trans-porter 3 (GLUT3) facilitates glucose transport in -to GB tumor cells. We aimed to explore the reg-ulation of GLUT3 in GB tumors of patients who were concurrently diagnosed with DM. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded (FFPE) tumor samples were collected from 93 GB patients and retrospective-ly analyzed. Of the total, 15 patients were con-currently diagnosed with DM (GB-DM). The role of GLUT3 in tumor aggressiveness was evalu-ated by analyzing its correlation with Ki67, P53 expression, !ALAT1 expression, and peripher-al blood hemoglobin A1C (HbA1c) level. T98G cells were treated with empagliflozin and met-formin to modulate GLUT3. The RNA expres-sion of GLUT3, SOX2, and !ALAT1 was analyzed by real-time qPCR. The lactate levels of T98G cells were measured by Cobas c502 analyzer. A scratch wound assay was performed to investi-gate the migration rate of T98G cells. RESULTS: GLUT3 expression was lower in GB-DM tumors than in GB-only tumors. In GB-DM, the expression of tumoral GLUT3 and pe-ripheral blood glycated hemoglobin (HbA1c) lev-els were negatively correlated with P53 and Ki67. A decreased GLUT3 shortened the disease-free survival duration in GB-DM patients. Empagli-flozin reduced GLUT3, while metformin-induced GLUT3 in T98G cells. The empagliflozin-medi-ated GLUT3 suppression induced SOX2 and !ALAT1 expressions and influenced the migra-tion capacity of T98G cells. CONCLUSIONS: Our findings suggest that the low GLUT3 expression of the tumors of GB-DM patients may induce the production of adenosine triphosphate (ATP) from cellular energy sources other than glucose metabo-lism. However, further studies are warranted to confirm these results.eninfo:eu-repo/semantics/closedAccessCell-growthCancerTransportersExpressionBrainGlut3MellitusPromotesObesityDiseaseDiabetes mellitusGlioblastomaHba1cGlucose metabolismGlut3Pharmacology & pharmacyArticle001089946700025811081182717