Abstract 15090: AMP-Activated Protein Kinase Upregulates Sodium-Dependent Glucose Transporter SGLT1, Which Contributes to Cardiac Ischemia-Reperfusion Injury

INTRODUCTION: AMP-activated protein kinase (AMPK) is cardioprotective during ischemia/reperfusion (I/R). We have identified a novel cardiac sodium glucose cotransporter, SGLT1, and determined that it is upregulated in transgenic mice with a mutation leading to AMPK hyperactivation. Therefore, we hypothesized that SGLT1 is a downstream target of AMPK and is involved in the cardiac response to I/R. METHODS AND RESULTS: HL-1 cells treated in vitro with the AMPK activator AICAR (1mM) for 24 h had a 2.89±0.6 fold increase in SGLT1 mRNA (vs. vehicle, N=3, P<0.01), which was abrogated by the AMPK inhibitor compound C (10 μM). Simulated ischemia in HL-1 cells with NaCN (5 mM for 4 h) increased SGLT1 expression 3.6±1.3 fold (N=5, P<0.005), which was abrogated by compound C. SGLT1 RNAi in HL-1 cells improved cell survival following 4 h of ischemia from 52±2% to 86±3% (P<0.002). Transgenic mice with cardiomyocyte-specific knockdown of SGLT1 (TGSGLT1-DOWN) and wildtype (WT) littermates were subjected to ex vivo globa...