The cardioprotective effect of inhibiting SGLT1 in hyperglycemia ischemia reperfusion injury

Abstract Background Diabetes clinical trials have shown SGLT inhibition improves cardiovascular outcomes, yet the mechanism is not fully understood. Hyperglycemia a common finding in diabetic and non-diabetic patients presenting with ACS powerful predictor of prognosis mortality. The role hyperglycemia ischemia-reperfusion injury (IRI) understood, whether Sodium Glucose Co-Transporter 1 (SGLT1) plays infarct augmentation, before and/or after reperfusion, remains to be elucidated. Purpose Investigate if SGLT1 involved glucotoxicity during IRI inhibiting an inhibitor may reduce size. Method RT-PCR in-situ hybridization (RNAScope) combined Immunofluorescence integrated co detection different cell marker techniques were used detect mRNA expression Sprague-Dawley whole myocardium isolated primary cardiomyocytes. An Ex-vivo Langendorff perfusion model was study effect high glucose (22mmol) on at reperfusion. Canagliflozin (CANA) non-selective (1μmoL/L block receptor SGLT2 5nmol/L only receptor) Mizagliflozin selective (100nmol/L) introduced following ischemia two concentration concentrations reperfusion its size measured using triphenyltetrazolium chloride (TTC) staining. Results We showed that homogenously expressed throughout particularly evident within vasculature. we demonstrate injurious increase myocardial infarction. Our data reveal exacerbation appears mediated via SGLT1. also demonstrated high-glucose isolated, perfused heart abrogated through administration clinically available mixed SGLT2/SGLT1 inhibitor, canagliflozin, dose inhibits both SGLT1, but by SGLT2-selective concentration. Conclusion present myocardium. augment infarction attenuates this incre Funding Acknowledgement Type funding sources: Private grant(s) Sponsorship. Main source(s): government saudi Arabia