Mechanistic exploration of hexokinase 2 and metabolism in diabetic cardiomyopathy

The pathogenesis of diabetic cardiomyopathy (DCM) remains incompletely understood. The present study employed weighted gene co‑expression network analysis to analyze the DCM transcriptome dataset from the Gene Expression Omnibus (GEO) database to identify genes associated with this disease. Subsequently, both internal and external validation of the expression of the characterized genes was performed using additional GEO datasets. Key DCM genes were validated at both the <i>in vitro</i> and <i>in vivo</i> levels by Western blot and immunohistochemistry, IHC). Furthermore, the mechanisms of gene and metabolite co‑expression in DCM were investigated through transcriptome sequencing of cells overexpressing disease‑associated genes, combined with quantitative measurements of metabolites. Notably, hexokinase 2 (HK2) was downregulated in both DCM cell and db/db mouse models. Low expression of HK2 was implicated in the disruption of organic acids and their derivatives, as well as the receptor for advanced glycation end‑products pathway.