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Physiological and molecular characterization of individuals carrying a diabetogenic mtDNA mutation establishes a mitochondrial basis for insulin resistance in humans

2025-12-19 endocrinology Title + abstract only
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Mitochondrial dysfunction has long been associated with insulin resistance, yet the causal relationship in humans remains unresolved. Here, we leveraged individuals carrying the diabetogenic m.3243A>G mtDNA mutation as a human genetic model to probe the causal contribution of mitochondrial defects to insulin resistance and delineate the underlying molecular and bioenergetic mechanisms. In vivo metabolic phenotyping revealed selective skeletal muscle insulin resistance with preserved liver and ad...

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