biostudies-literatureUnknown7Zhang HChina Scholarship CouncilEuropean Association for the Study of Diabetes<b>Aims/hypothesis:</b> Changes in cardiac metabolism and ion homeostasis precede and drive cardiac remodeling and heart failure development. We previously demonstrated that sodium/glucose cotransporter 2 inhibitors (SGLT2i's) have direct cardiac effects on ion homeostasis, possibly through inhibition of the cardiac sodium/hydrogen exchanger (NHE-1). Here, we hypothesize that Empagliflozin (EMPA) also possesses direct and acute cardiac effects on glucose and fatty acid metabolism of isolated type II diabetes mellitus (<i>db/db</i>) mouse hearts. In addition, we explore whether direct effects on glucose metabolism are nullified in the presence of an NHE-1 inhibitor. <b>Methods:</b> Langendorff-perfused type II diabetic db/db mouse hearts were examined in three different series: <b>1</b>: <sFrontiers in cardiovascular medicine592233https://www.ebi.ac.uk/biostudies/studies/S-EPMC7746656biostudies-literatureEmpagliflozin Decreases Lactate Generation in an NHE-1 Dependent Fashion and Increases α-Ketoglutarate Synthesis From Palmitate in Type II Diabetic Mouse Hearts.PMC7746656Uthman LBakker DHouten SMSari SZhang HCoronel RHollmann MWChen SZuurbier CJWeber NCvan Weeghel MfalseEmpagliflozin Decreases Lactate Generation in an NHE-1 Dependent Fashion and Increases α-Ketoglutarate Synthesis From Palmitate in Type II Diabetic Mouse Hearts.<b>Aims/hypothesis:</b> Changes in cardiac metabolism and ion homeostasis precede and drive cardiac remodeling and heart failure development. We previously demonstrated that sodium/glucose cotransporter 2 inhibitors (SGLT2i's) have direct cardiac effects on ion homeostasis, possibly through inhibition of the cardiac sodium/hydrogen exchanger (NHE-1). Here, we hypothesize that Empagliflozin (EMPA) also possesses direct and acute cardiac effects on glucose and fatty acid metabolism of isolated type II diabetes mellitus (<i>db/db</i>) mouse hearts. In addition, we explore whether direct effects on glucose metabolism are nullified in the presence of an NHE-1 inhibitor. <b>Methods:</b> Langendorff-perfused type II diabetic db/db mouse hearts were examined in three different series: <b>1</b>: <s2020-01-01T00:00:00Z20202025-06-01T00:20:31.708Z2025-06-01T00:20:31.708ZS-EPMC77466563334451810.3389/fcvm.2020.592233