3.4.2 Ferroptosis may mediate insulin resistance
ACSL4 is another important factor in the occurrence of ferroptosis, and
its increase will enhance lipid peroxidation and promote the production
of more lipid peroxides, finally leading to the ferroptosis of
cells108. Up-regulation of ACSL4 expression was
observed in mice fed a high-fat
diet(HD). In the same study, adipocyte-specific ACSL4 knockout mice were
found to be protected from HD-induced cell death and insulin
resistance109. Another experiment showed that ACSL4
protein is present in human and rat islet β cells, concentrated around
insulin secretory granules and mitochondria, and participates in insulin
secretion by modifying fatty acids in insulin secretory granules and
mitochondria110. These findings suggest that ACSL4 may
promote insulin secretion in beta cells, but it may exacerbate
peripheral insulin resistance. Therefore, more experiments on the
function of ACSL4 are needed to explore whether ACSL4 mediates
ferroptosis and plays an important role in the pathogenesis of DM and
whether targeting ACSL4 can prevent and treat DM.