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 CONCLUSIONS: AMPK is an upstream regulator of cardiac SGLT1. Although AMPK generally mediates cardioprotection in I/R, transgenic knockdown of SGLT1 in mice improved post-I/R functional recovery, decreased infarction size, and decreased oxidative stress. These effects may be related to decreased oxidative stress. SGLT1 may be a novel therapeutic interventional target for ischemic heart disease.