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.