Background: Recently, we reported Na+/glucose co-transporter (SGLT1) expression in mouse and human heart. We speculated that SGLT1 might play an important role in ischemic preconditioning-induced cardioprotection. Therefore, the present study was designed to find the role of SGLT1 in ischemic preconditioning-induced cardioprotection.
Methods: Hearts isolated from SD male rats were subjected to either ischemia-reperfusion injury (I/R) (15 min global ischemia followed by 20 min reperfusion) or ischemic preconditioning (IPC) (3 cycles of 2 min global ischemia separated by 3 min reperfusion) followed by I/R in presence and absence of phlorizin, an SGLT1 inhibitor.
Results: IPC increased membrane SGLT1 expression in rat heart as observed by immunoblotting and immunohistochemistry. Hearts from I/R group showed significant increase in oxidative stress levels and marked myocardial injury as compared to control. We also observed significant increase in apoptotic parameters in I/R heart, as measured by caspase-3 activity, TUNEL positive nuclei and gene expression analysis. Significant improvement in oxidative stress, apoptosis parameters and cardiac injury was observed in I/R hearts when subjected to IPC. However, all beneficial effects of preconditioning were lost when hearts were pre-treated with phlorizin.
Conclusion: Present study indicated that inhibition of SGLT1 by phlorizin abrogated the beneficial effect of ischemic-preconditioning and for the first time, provides evidence that SGLT1 plays a crucial role in ischemic preconditioning-induced cardioprotection.
Keywords: Ischemia-reperfusion injury; Oxidative stress; Phlorizin; Preconditioning; SGLT1.
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