Microvascular insulin resistance with enhanced muscle glucose disposal in CD36 deficiency
Authors' conclusion
CD36 deficiency was previously shown to reduce muscle/heart fatty acid uptake, whereas here we showed that it reduced vascular compliance and the ability of insulin to increase MBV for optimising glucose and oxygen delivery. The muscle and heart respond to these energy challenges by transcriptional remodelling priming the tissue for insulin-stimulated glycolytic flux. Reduced oxygen delivery activating hypoxia-induced factors, endothelial release of growth factors or small intracellular vesicles might mediate this adaptation. Targeting NO bioavailability in CD36 deficiency could benefit the microvasculature and muscle/heart metabolism.
Study context
- Population
- Cd36-/- and wild-type mice; individuals with 50% CD36 deficiency (rs3,211,938 G allele carriers) and controls; primary human microvascular endothelial cells with/without CD36 depletion
- Comparison
- CD36 deficiency vs control
- Outcome
- Insulin-stimulated glucose disposal and microvascular insulin response
Methodological detailsmulti-disciplinary, hyperinsulinaemic-euglycaemic clamps, mouse, human and cell studies
- Multi-disciplinary
- Hyperinsulinaemic-euglycaemic clamps
- Mouse, human and cell studies
Main finding
As reported in the abstract
- Cd36-/- mice: enhanced insulin-stimulated glucose disposal but reduced vascular compliance and capillary perfusion
- Cd36-/- mice: unaltered transcapillary insulin flux (gastrocnemius)
- CD36-deficient humans: better insulin-stimulated glucose disposal but insulin-unresponsive microvascular blood volume (MBV)
- CD36-depleted human microvascular cells: impaired insulin activation of Akt, endothelial NO synthase and NO generation
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Original publication
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