Conclusions
Our findings showed that diabetes increased oxidative stress to exacerbate liver IR injury by impairing 5' adenosine monophosphate-activated protein kinase-mediated mitophagy. Strategies targeting oxidative stress and mitophagy might provide a promising approach to ameliorate liver IR injury in diabetes patients.
Methods
Wild-type and db/db (DB) mice were subjected to a partial warm liver IR model. Liver injury, oxidative stress, mitophagy and related molecular pathways were analyzed.
Results
Here, we found that increased liver IR injury was observed in DB mice, as evidenced by higher levels of serum alanine aminotransferase and serum aspartate, worsened liver architecture damage and more hepatocellular death. DB mice also showed increased mitochondrial oxidative stress. Mitochondrial reactive oxygen species scavenge alleviated liver IR injury in DB mice. Mechanistic analysis showed that 5' adenosine monophosphate-activated protein kinase-mediated mitophagy was suppressed in DB mice post-IR. Pharmacological activation of 5' adenosine monophosphate-activated protein kinase by its agonist effectively restored mitophagy activation, leading to decreased mitochondrial oxidative stress and attenuated liver IR injury in DB mice. Conclusions: Our findings showed that diabetes increased oxidative stress to exacerbate liver IR injury by impairing 5' adenosine monophosphate-activated protein kinase-mediated mitophagy. Strategies targeting oxidative stress and mitophagy might provide a promising approach to ameliorate liver IR injury in diabetes patients.