Concurrent presence of diabetes affects the<i> GLUT3</i> programming of glucose metabolism in glioblastoma


Kocaeli A. A., Tekin C., Ercelik M., Tezcan G., Aksoy S., Kocaeli H., ...Daha Fazla

EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES, cilt.27, sa.17, ss.8110-8118, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 27 Sayı: 17
  • Basım Tarihi: 2023
  • Doi Numarası: 10.26355/eurrev_202309_33571
  • Dergi Adı: EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE, Directory of Open Access Journals
  • Sayfa Sayıları: ss.8110-8118
  • Anahtar Kelimeler: Diabetes mellitus, Glioblastoma, Glucose metabolism, GLUT3, HbA1c
  • Bursa Uludağ Üniversitesi Adresli: Evet

Özet

OBJECTIVE: 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.