Ferroptosis inhibition is a new treatment mechanism of high-intensity interval training in Type 2 diabetes mellitus

Abstract

Background: A recent discovery is the connection between ferroptosis and type 2 diabetic mellitus (T2DM). However, while earlier research has demonstrated the beneficial effects of HIIT on type 2 diabetes, its potential mechanisms remain unclear. In the current work, we examined the impact of HIIT on glucose, insulin levels, lipid profile, and the SIRT1/Nrf2/GPx4 pathway, which is a crucial regulatory molecule in the process of ferroptosis in streptozotocin-induced diabetic rats.

Methods: Three sets of streptozotocin-induced diabetes-specified-pathogen-free (SPF) SD rats were created: diabetic + HIIT, diabetic, and control. To measure the serum concentrations of insulin, glucose, and lipid profiles, blood samples were obtained. To evaluate the expression of the genes linked to pancreatic ferroptosis, real-time PCR was used. Additionally, pancreatic tissue's ferroptosis-related enzyme activity was evaluated.

Results: Compared to CON rats, the T2DM group showed a significant decrease in the mRNA levels of ferroptosis-related genes, such as SIRT1, Nrf2, and GPx4. In T2DM+HIIT, the expression of these ferroptosis-related genes was markedly elevated. Moreover, GPx4, Nrf2, and SIRT1 G6PD, 6PGDH, SIRT1, Nrf2, and GPx4 enzyme activities in pancreatic tissue were significantly reduced by STZ-induced diabetes; however, these enzyme activities were significantly increased in diabetic rats treated with HIIT.

conclusion:  we started by talking about how HIIT affected T2DM metabolic metrics. Next, by altering the ferroptosis pathway, we investigated how HIIT was regulated in T2DM rats. Furthermore, through both direct (through the SIRT1/Nrf2/GPx4 pathway) and indirect (by PPP enzymes) suppression of ferroptosis, HIIT enhanced pancreatic function.