Inhibition of SGLT2 Rescues Bone Marrow Cell Traffic for Vascular Repair: Role of Glucose Control and Ketogenesis

The mechanisms by which sodium–glucose cotransporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in people with diabetes are incompletely understood. Recent studies show that SGLT2i may increase the levels of circulating cells vascular regenerative capacity, at least part lowering glycemia. In this study, we used mice streptozotocin-induced treated dapagliflozin a dose reduced glucose 20%. Dapagliflozin improved diabetes-associated defect hematopoietic stem cell mobilization after stimulation granulocyte colony-stimulating factor. rescued traffic bone marrow (BM)–derived to injured carotid arteries and endothelial healing diabetic mice. Defective homing CD49d+ granulocytes was causally linked impaired repair reversed dapagliflozin. effects were mimicked similar extent reduction achieved insulin therapy ketone drink artificially elevated ?-hydroxybutyrate. Inhibition resident using CXCR4 antagonist AMD3100 did not abolish effect dapagliflozin, indirectly supporting mediated recruitment cells. summary, BM-derived site injury, providing hitherto unappreciated mechanism protection.