Concurrent presence of diabetes affects the GLUT3 programming of glucose metabolism in glioblastoma.

Diabetes mellitus (DM)-mediated impaired glucose metabolism increase in the glioblastoma (GB) risk by inducing hyperglycemia and hyperinsulinemia. An integral membrane transport protein, glucose transporter 3 (GLUT3) facilitates glucose transport into GB tumor cells. We aimed to explore the regulation of GLUT3 in GB tumors of patients who were concurrently diagnosed with DM.Formalin-fixed paraffin-embedded (FFPE) tumor samples were collected from 93 GB patients and retrospectively analyzed. Of the total, 15 patients were concurrently diagnosed with DM (GB-DM). The role of GLUT3 in tumor aggressiveness was evaluated by analyzing its correlation with Ki67, P53 expression, MALAT1 expression, and peripheral blood hemoglobin A1C (HbA1c) level. T98G cells were treated with empagliflozin and metformin to modulate GLUT3. The RNA expression of GLUT3, SOX2, and MALAT1 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 investigate the migration rate of T98G cells.GLUT3 expression was lower in GB-DM tumors than in GB-only tumors. In GB-DM, the expression of tumoral GLUT3 and peripheral blood glycated hemoglobin (HbA1c) levels were negatively correlated with P53 and Ki67. A decreased GLUT3 shortened the disease-free survival duration in GB-DM patients. Empagliflozin reduced GLUT3, while metformin-induced GLUT3 in T98G cells. The empagliflozin-mediated GLUT3 suppression induced SOX2 and MALAT1 expressions and influenced the migration capacity of T98G cells.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 metabolism. However, further studies are warranted to confirm these results.