High Glucose Sensitizes Male and Female Rat Cardiomyocytes to Wnt/β-Catenin Signaling

Wnt/β-catenin signaling has been shown to regulate gene expressions in cardiomyocytes. However, it is not known if this effect is dependent on the sex of cells or the glucose level in the culture medium. In the present study, ventricular myocytes were prepared from male and female neonatal rats and maintained in either a glucose-rich (25 mM) medium or a low-glucose (3 mM), lipid-rich medium. Real-time quantitative PCR was used to measure changes in target genes (<i>Axin2</i>, <i>Scn5a,</i> and <i>Tbx3</i>) after treatment with 1, 3, or 10 µM of CHIR-99021, an activator of Wnt/β-catenin signaling. CHIR induced similar changes in <i>Axin2, Tbx3, and Scn5a</i> transcripts in male and female NRVMs in both media, suggesting the absence of sex difference. However, cells in a high-glucose medium showed greater increases in <i>Axin2</i> and <i>Tbx3</i> transcripts than cells in a low-glucose medium. In addition, a low concentration of CHIR (1 µM) reduced the <i>Scn5a</i> transcript in cells in a high-glucose medium but not in a low-glucose medium, suggesting an increased sensitivity to Wnt signaling by high glucose. A non-linear relationship was identified between <i>Axin2</i> transcript upregulation and <i>Scn5a</i> transcript downregulation in CIHR-treated NRVMs. These data suggest that high glucose sensitizes both male and female cardiomyocytes to Wnt/β-catenin signaling.