Type-2 diabetic rat heart: The effect of kolaviron on mTOR-1, P70S60K, PKC-α, NF-kB, SOD-2, NRF-2, eNOS, AKT-1, ACE, and P38 MAPK gene expression profile

It has been established that genetic factors partially contribute to type-2 diabetes and vascular disease development. This study determined the effect of kolaviron on the expression profile of genes associated with the insulin signaling pathway and involved in regulating glucose and lipid metabolism, oxidative stress, inflammation, vascular functions, pro-survival and the apoptosis pathway in the heart of type-2 diabetic rats. After induction and confirmation of type-2 diabetes seven days after, the rats were treated with kolaviron for twenty-eight days before being euthanized. Organs were harvested and stored at - 80 °C in a biofreezer. Total RNA was extracted from the ventricle, reverse transcribed to cDNA followed by a real-time quantitative polymerase chain reaction (RT-qPCR) analysis of the expression of mTOR-1, P70S60K, PKC-α, NF-kB, SOD-2, NRF-2, eNOS, AKT-1, ACE, p38 MAPK and the reference gene (GAPDH), after which they were normalized/standardized. The results show an increase in the relative mRNA expression of mTOR/P70S60K/PKCα /P38MAPK/NF-KB/ACE and a decrease in the relative mRNA expression of NRF2/SOD/AKT/eNOS in the heart of the diabetic rats. Nevertheless, kolaviron modulated the expression profile of these genes, which suggest a therapeutic effect and target for vascular dysfunction and complications in type-2 diabetes through the activation of the NRF-2/AKT-1/eNOS signaling pathway and suppression of the NF-kB/PKC signaling pathway.