Reducing the mitochondrial oxidative burden alleviates lipid-induced muscle insulin resistance in humans.

ABSTRACT: Preclinical models suggest mitochondria-derived oxidative stress as an underlying cause of insulin resistance. However, it remains unknown whether this pathophysiological mechanism is conserved in humans. Here, we used an invasive in vivo mechanistic approach to interrogate muscle insulin action while selectively manipulating the mitochondrial redox state in humans. To this end, we conducted insulin clamp studies combining intravenous infusion of a lipid overload with intake of a mitochondria-targeted antioxidant (mitoquinone). Under lipid overload, selective modulation of mitochondrial redox state by mitoquinone enhanced insulin-stimulated glucose uptake in skeletal muscle. Mechanistically, mitoquinone did not affect canonical insulin signaling but augmented insulin-stimulated glucose tra

SUBMITTER: Fiorenza M 

PROVIDER: S-EPMC11524190 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature