Hormonal
Acute elevation of plasma free fatty acids (FFA) induces insulin resistance in human skeletal muscle by inhibiting insulin-stimulated glucose transport activity, rather than glucose phosphorylation.
High levels of free fatty acids in your blood (often from high fat intake or obesity) can block insulin's ability to move glucose into your muscles. This happens because fat interferes with the insulin signaling pathway (PI 3-kinase) before glucose can be used. Managing blood fat levels through diet and exercise can help restore this sensitivity.
Taken together, these data suggest that increased concentrations of plasma FFA induce insulin resistance in humans through inhibition of glucose transport activity; this may be a consequence of decreased IRS-1–associated PI 3-kinase activity.
Why this rating
High-quality human clinical trial using gold-standard hyperinsulinemic-euglycemic clamps and NMR spectroscopy, though limited to healthy young subjects.
Source
Effects of free fatty acids on glucose transport and IRS-1–associated phosphatidylinositol 3-kinase activity
Alan Dresner et al. · Journal of Clinical Investigation · 1999
DOI 10.1172/jci5001
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