Iron dysregulation, ferroptosis, and oxidative stress in diabetic osteoporosis: Mechanisms, bone metabolism disruption, and therapeutic strategies

Figure 2 The process of iron absorption in the small intestine. Iron is primarily absorbed in the upper small intestine through an energy-dependent active transport process involving two key steps: Uptake of iron from the intestinal lumen by mucosal cells and its subsequent transport into the plasma. This process requires the participation of multiple transport proteins. Divalent metal transporter 1, located on the apical membrane of mucosal cells, facilitates the H⁺-dependent active transport of Fe²⁺ into intestinal epithelial cells. On the basolateral membrane, FPN1 mediates the export of Fe²⁺ from the cells into the bloodstream, also via an H⁺-dependent mechanism. Any inorganic iron that remains within the mucosal cells without being exported can be oxidized to Fe³⁺ and stored temporarily as ferritin by binding to apoferritin. This stored iron is slowly released into the bloodstream over time. Iron that is not utilized is eventually lost with the natural turnover and shedding of mucosal cells, preventing excessive accumulation. This sophisticated balance ensures efficient iron absorption by the intestinal mucosa while protecting the body from iron overload. Under normal conditions, iron homeostasis is regulated by hepcidin, a liver-secreted hormone that modulates iron availability. Elevated ROS can further promote iron release and increase its bioavailability, potentially exacerbating iron overload. DMT1: Divalent metal transporter 1; FPN1: Ferroportin 1; ROS: Reactive oxygen species.