Hormonal
Mitochondrial dysfunction, characterized by impaired oxidative capacity and increased reactive oxygen species (ROS), promotes insulin resistance in skeletal muscle by causing the accumulation of lipotoxic lipid intermediates (diacylglycerol and ceramide) that inhibit insulin signaling.
For those with insulin resistance or T2DM, focusing on interventions that support mitochondrial health (like exercise which upregulates PGC-1α) may be more effective than focusing solely on caloric restriction. The paper suggests that boosting mitochondrial function can improve insulin sensitivity, potentially by reducing toxic lipid buildup in muscles.
A decrease in metabolic substrate oxidation appears as a primary defect, which, by triggering a cascade of events culminating with the intracellular accumulation of the diacylglycerol and ceramide, hampers insulin signalling and promotes insulin resistance.
Why this rating
The paper reviews extensive human and animal studies, including microarray data and in vivo assessments, though noting conflicting evidence.
Source
Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet
Domenico Sergi et al. · Frontiers in Physiology · 2019
DOI 10.3389/fphys.2019.00532
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