Sodium butyrate and voluntary exercise through activating VEGF-A downstream signaling pathway improve heart angiogenesis in type 2 diabetes

Background: Inadequate angiogenesis in patients with type 2 diabetic heart could result in deprived collateral formation. Herein, we aimed to investigate the effects of sodium butyrate (NaB) along with voluntary exercise simultaneously on the mechanisms acting on cardiac angiogenesis.Materials and methods: Animals were divided into the following five groups: control (Con), diabetic rats (Dia), diabetic rats treated with NaB (200 mg/kg, i.p.) (Dia-NaB), diabetic rats receiving voluntary exercise (Dia-Exe), and diabetic rats treated with NaB and exercise simultaneously (Dia-NaB-Exe). After an eight-week duration, NO metabolites levels were measured using Griess method, the VEGF-A and VEGFR2 expressions was examined by PCR, the expressions of VEGF-A and VEGFR2 proteins was investigated by western blot, and ELISA method was used for Akt, ERK1/2 expression.Results: Cardiac VEGF-A and VEGFR2 expressions were higher in the Dia-Exe and Dia-NaB-Exe groups compared to the Dia group. However, a combination of exercise and NaB enhanced the VEGF-A expression in cardiac tissue compared to the Dia-NaB and Dai-Exe groups. Heart NOx concentration was higher in the treated groups compared to the Dia group. The expression of cardiac Akt levels increased in both the Dia-Exe and Dia-NaB-Exe groups compared to the Dia groups. In addition, cardiac ERK1/2 expression was found to be higher in the DiaNaB-Exe group compared to the Dia group.Conclusion: The findings of this study showed the therapeutic potential of a novel combination therapy of sodium butyrate and voluntary exercise in improving cardiac angiogenesis with the enhanced involvement mechanism in high fat/STZ-induced type 2 diabetic rats.