GSE125451
Diabetes severity is reflected by changes in a cardiac gene expression signature characterized by metabolism and cell death processes
We tested the impact of a graded reduction in insulin on cardiac gene expression with particular focus on metabolism and energy homeostasis. Wistar rats were made diabetic with a single dose of either 55 (D55) or 100 (D100) mg/kg streptozotocin (STZ). Although both D55 and D100 were equally hyperglycemic compared to control, D100 showed markedly lower plasma insulin and robust increases in plasma FA and TG. D100 demonstrated more significant transcriptomic changes than D55 with enrichment for metabolic processes that direct the heart to use FA, when glucose use is obstructed. Analysis of a protein-protein interaction network identified functional networks in D100 that describe mitochondrial overload, incomplete fatty acid oxidation, and loss of cardiomyocytes. Our data suggests that the differential reduction of insulin produced a dramatic change in cardiac gene expression largely enriched for substrate metabolism functions as well as a gene expression program supporting cell death. Overall design: We analyzed 4 control samples, 6 D55 samples and 6 D100 samples with RNA-Seq.