Sodium-glucose Co-transporter 2 (SGLT2) inhibitor dapagliflozin acutely activates cardiomyocyte HIF-1α signaling via succinate, a signaling metabolite - PubMed
4 days ago
- #heart failure
- #SGLT2 inhibitors
- #HIF-1α signaling
- SGLT2 inhibitors like dapagliflozin are used for chronic and acute heart failure, but mechanisms are unclear.
- Short-term dapagliflozin treatment activates HIF-1α signaling in cardiomyocytes, mediated by ketone body-derived succinate.
- HIF-1α target gene upregulation by dapagliflozin was abolished in cardiomyocyte-specific HIF-1α knockout mice.
- Metabolome analysis showed increased ketone body levels and succinate accumulation in the heart after dapagliflozin treatment.
- SCOT inhibitor pimozide blocked dapagliflozin-induced HIF-1α signaling activation.
- Study suggests HIF-1α may play a role in SGLT2 inhibitor effects and could be a future research target.