Table 1.
Selected studies exploring links between mitochondrial dysfunction and insulin resistance
| Sample group | Observation | Reference |
|---|---|---|
| Young, IR offspring of parents with T2DM | Decreased mitochondrial activity, increased intramyocellular FA, and lower ratio of type 1 to type 2 fibers in muscle. | (45) |
| Reduced mitochondrial density in muscle of IR offspring of T2DM parents. | (46, 47) | |
| Overweight/obese individuals | Improved IR without increasing mitochondrial capacity. | (63) |
| Elderly, lean individuals | Severe IR in skeletal muscle, with decreased mitochondrial oxidative capacity, and decreased ATP synthesis. | (52) |
| T2DM patients/IR individuals | Mitochondrial fatty acid oxidation normal. | (64) |
| Mitochondrial dysfunction in IR, 30%-40% lower mitochondrial enzyme activity. | (44, 53, 65, 66) | |
| PGC 1α-dependent genes involved in oxidative metabolism are downregulated in skeletal muscle of individuals with family history of T2DM and T2DM patients compared to healthy controls. | (67) | |
| Increased daily physical activity improves lipid oxidation independent of change in mitochondrial activity in people with T2DM. | (68) | |
| IR Asian Indians with T2DM showed muscle mitochondrial capacity similar to nondiabetic Indians, but higher than Northern European Americans. Asian Indians have greater IR than Northern Europeans. | (69) | |
| Obese diabetic and normal males showed altered activities of enzymes involved in carbohydrate breakdown, and aerobic metabolism in muscle. | (70) | |
| T2DM patients have normal muscle mitochondrial function. | (71) | |
| Rodent studies | High-fat diet reduces mitochondrial gene expression in muscle. | (72) |
| Decreased mitochondrial function does not cause IR in mice. | (73) | |
| UCP-mediated energy depletion increases glucose uptake despite reduced mitochondrial function. | (74) | |
| High-fat diet causes IR but increases mitochondrial capacity. | (75-77) | |
| Lowering plasma FFA reduces mitochondrial gene expression in muscle. | (78) |
Abbreviations: ATP, adenosine 5′-triphosphate; FA, fatty acid; FFA, free fatty acid; IR, insulin resistance; PGC1α, peroxisome proliferator-activated receptor gamma coactivator 1-alpha; T2DM, type 2 diabetes mellitus; UCP, uncoupling protein.