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Hypoxia exacerbates this process through an independent mechanism

( Zhou Z, Bian C, Luo Z, et al

Impaired insulin signaling Insulin signaling plays a crucial role in maintaining peripheral nerve health, and its impairment significantly contributes to the pathogenesis of DPN

Moreover, melatonin activates pyruvate dehydrogenase kinase 4 (PDK4) to regulate acetyl-CoA content ( -oxidation or increasing the transfer of fatty acid-derived acetyl-CoA into mitochondria ( FIGURE 2 Second, melatonin can enhance the activity of the electron-transport chain (ETC) and oxidative phosphorylation (OXPHOS) to regulate mitochondrial metabolism