High palmitate induces ferroptosis in RIN-m5f cells via miR-3584-5p-mediated suppression of AQP7.

Aquaporin-7 (AQP7) is a crucial aquaporin in pancreatic islet β-cells, acting as a crucial role in sustaining cellular viability and survival. An in vitro model was employed, specifically RIN-m5f islet β-cells exposed to elevated levels of palmitic acid, to investigate the influence of high-lipid conditions on AQP7 expression and its associated downstream effects. Our findings demonstrated a marked reduction in AQP7 expression, coupled with heightened activation of oxidative stress markers and ferroptosis pathways. Notably, the downregulation of AQP7 was linked to elevated concentrations of reactive oxygen species (ROS) and lipid peroxidation, leading to impaired β-cell function. Moreover, we observed that the upregulation of miR-3584-5p under high-lipid conditions contributed to the inhibition of AQP7, thereby exacerbating oxidative stress and promoting ferroptosis. Inhibition of miR-3584-5p restored AQP7 levels, alleviated oxidative stress and improved β-cell viability. These findings reveal a novel mechanism through which AQP7 influences cellular oxidative stress and ferroptosis, emphasizing its crucial regulatory role in preserving β-cell health in high-lipid environments. Additionally, the study emphasizes the potential of targeting AQP7 and related pathways as therapeutic strategies to mitigate high-lipid-induced pancreatic β-cell injury.