| First Author | Chen Z | Year | 2023 |
| Journal | Eur J Pharmacol | Volume | 945 |
| Pages | 175552 | PubMed ID | 36739076 |
| Mgi Jnum | J:361006 | Mgi Id | MGI:7855093 |
| Doi | 10.1016/j.ejphar.2023.175552 | Citation | Chen Z, et al. (2023) Characterization of the effect of the GLUT-1 inhibitor BAY-876 on T cells and macrophages. Eur J Pharmacol 945:175552 |
| abstractText | Increased aerobic glycolysis is a metabolic hallmark of proinflammatory leukocytes including macrophages and T cells. To take up glucose from the environment and fuel glycolysis, activated leukocytes upregulate the glucose transporter GLUT1. The orally bioavailable selective GLUT1 inhibitor BAY-876 was developed primarily as an anti-tumor drug. Our study assessed its activity on activated macrophages and CD4(+) T cells. BAY-876 significantly attenuated glucose uptake by cultured CD4(+) T cells and macrophages by 41% and 15%, respectively. Extracellular flux analysis of activated CD4(+) T cells in vitro showed that BAY-876 significantly decreases glycolytic proton flux rate and lactate production, effects that are accompanied by an increased oxidative phosphorylation-mediated ATP production rate, leaving intracellular ATP levels per cell unchanged. However, GLUT1 inhibition reduced CD4(+) T cell proliferation without compromising cell viability and reduced IFN-gamma secretion by 20%. Moreover, TNF secretion from macrophages was reduced by 27%. We conclude that GLUT1-specific inhibitors, like BAY-876, deserve further in vivo testing in a broad range of (auto-) inflammatory disease models. |
