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

OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. 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 metabolism. However, further studies are warranted to confirm these results.

Association Between Resistance to Cinacalcet and Parathyroid Gland Hyperplasia in Kidney Transplant Recipients with Persistent Hypercalcemia.

BACKGROUND: Persistent hypercalcemia and hyperparathyroidism after successful kidney transplantation can be detrimental in some recipients and should be ameliorated. OBJECTIVE: To point out the concerns regarding resistance to cinacalcet in kidney transplant recipients with persistent hypercalcemia. METHODS: 14 renal transplant recipients who received cinacalcet treatment because of persistent hypercalcemia were included in the study. Serum creatinine, estimated glomerular filtration rate (eGFR), calcium, phosphorus, and intact parathyroid hormone (PTH) levels at the baseline and throughout the treatment, and ultrasonography and parathyroid scintigraphy findings were recorded. RESULTS: Cinacalcet treatment was initiated after a mean±SD of 20.7±19.7 months of transplantation and maintained for 16.9±7.9 months. Serum calcium levels were significantly decreased with the cinacalcet treatment. There were no significant changes in serum creatinine, eGFR, phosphorus, and PTH levels. In all participants, serum calcium levels were increased from 9.8±0.6 to 11.1±0.6 mg/dL (p<0.001) within 1 month of cessation of cinacalcet. 7 recipients with adenoma-like hyperplastic glands underwent parathyroidectomy (PTx) due to failure with cinacalcet. CONCLUSION: Cinacalcet may be an appropriate treatment for a group of recipients with hypercalcemia without adenoma-like hyperplastic glands or who had a contraindication for surgery. Recipients with enlarged parathyroid gland may resist to cinacalcet-induced decrease in serum PTH, although the concomitant hypercalcemia may be corrected.