3.4.1 Ferroptosis may mediate islet β-cell dysfunction
Islet beta cell dysfunction plays an important role in the occurrence and development of diabetes. It has been proposed that pancreatic β-cells have low expression levels of the antioxidant enzymes superoxide dismutase (SOD), glutathione (GSH) peroxidase, and catalase106, which suggests that they are susceptible to oxidative stress and thus ferroptosis. Killion et al107. observed small atrophy of mitochondria, increased membrane density, and disappearance of mitochondrial crista in pancreatic islet β cells of T2DM mice, and iron deposition in or near the center of the islet, which was consistent with typical changes of ferroptosis, further suggesting that ferroptosis may mediate the dysfunction of pancreatic islet β cells.When the iron homeostasis in pancreatic β cells is destroyed, a large amount of iron accumulates in the cells. Excessive free reactive Fe2+ can produce lipid peroxides through catalyzing lipid peroxidation, and form ROS through the Fenton reaction. Due to the lack of antioxidant enzymes expressed by pancreatic β cells themselves, ROS and lipid peroxides cannot be eliminated in time, and a large accumulation may cause ferroptosis. Make the islet cell differentiation disorder and even death, resulting in reduced insulin secretion. In vitro studies, erastin, an iron death inducer, was associated with significantly reduced insulin secretion and impaired islet function. Pretreatment with ferroptosis inhibitor ferrostatin-1 or DFO rescued the above injury8. These findings suggest that ferroptosis may mediate islet β-cell dysfunction.