Gene Expression Analysis Of Glycemic Memory In Heart Failure

Diabetes is a growing epidemic, with 37.3 million affected in the US. Diabetic patients are twice as likely to develop cardiovascular disease (CVD). Risk of CVD persists for years even following restoration of glycemic control in type-2-diabetic patients. These findings led to the hypothesis of glycemic memory, i.e., prior changes in glucose levels and delivery may lead to long-term molecular changes predisposing patients to CVD. We proposed that prior enhanced cellular glucose uptake leads to transcriptional changes that contribute to glycemic memory and enhances susceptibility to heart failure. We used a mouse model of doxycycline (DOX)-inducible cardiomyocyte-restricted glucose transporter 4 (GLUT4; mG4H), where mG4H is overexpressed for 2 wk (ON) and then returned to basal levels (OFF). Harvested left ventricular tissues from 4 groups of male mice (n=3) - ON and matched control (Con), OFF and DOX-matched Con (DCon) - were subjected to RNA sequencing analysis (Adjusted P <0.1, Fold-Change>