The SGLT2-inhibitor dapagliflozin improves neutropenia and neutrophil dysfunction in a mouse model of the inherited metabolic disorder GSDIb.
Mol Genet Metab Rep
; 29: 100813, 2021 Dec.
Article
em En
| MEDLINE
| ID: mdl-34712576
Glycogen Storage Disease type 1b (GSDIb) is a genetic disorder with long term severe complications. Accumulation of the glucose analog 1,5-anhydroglucitol-6-phosphate (1,5AG6P) in neutrophils inhibits the phosphorylation of glucose in these cells, causing neutropenia and neutrophil dysfunctions. This condition leads to serious infections and inflammatory bowel disease (IBD) in GSDIb patients. We show here that dapagliflozin, an inhibitor of the renal sodium-glucose co-transporter-2 (SGLT2), improves neutrophil function in an inducible mouse model of GSDIb by reducing 1,5AG6P accumulation in myeloid cells.
1,5-anhydroglucitol-6-phosphate; 1,5AG, 1,5-anhydroglucitol; 1,5AG6P, 1,5-anhydroglucitol-6-phosphate; BM, bone marrow; CFU, colony forming units; Dapagliflozin; G-CSF, granulocyte colony stimulating factor; G6PC3, glucose-6-phosphatase C3; G6PT, glucose-6-phospate translocase; GSDIb, Glycogen Storage Disease type 1b; Glycogen storage disease type 1b; M-CSF, macrophage colony stimulating factor; Mouse model; NET, neutrophil extracellular trap; Neutrophils; PMA, phorbol myristate acetate; PRM, parallel reaction monitoring; Renal sodium-glucose co-transporter-2; SGLT2, sodium-glucose co-transporter-2; TM, tamoxifen; fMLP, N-formyl-L-methionyl-L-leucyl-phenylalanine
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MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article