Research
Hormonal
Medium plasma FFA concentrations reduce glycogen synthesis by impairing glucose transport or phosphorylation, leading to decreased glucose-6-phosphate levels, before glycogen synthase activity is affected.
Even moderate levels of fat in your blood can interfere with how your muscles take up and process glucose, before they affect the enzyme that stores it as glycogen. This happens by reducing the amount of glucose-6-phosphate, a key intermediate.
GoodSupportsHIGH confidence
The second defect, which preceded the glycogen synthase defect, was seen at medium (~550 uM) FFA concentration, was associated with a decrease in muscle glucose-6-phosphate concentration, and was probably due to a reduction in glucose transport/phosphorylation.
Why this rating
Controlled human clinical trial with muscle biopsies.
Source
Mechanisms of fatty acid-induced inhibition of glucose uptake.
G Boden et al. · Journal of Clinical Investigation · 1994
DOI 10.1172/jci117252
rct · n=14Cited 3,473×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- Elevated plasma free fatty acid (FFA) concentrations cause a dose-dependent inhibition of insulin-stimulated glucose uptake in skeletal muscle, primarily by reducing glycogen synthesis and secondarily by reducing carbohydrate oxidation.Good
- Elevated plasma free fatty acids (FFA) and/or glycerol increase hepatic glucose output (HGO) by approximately 50%, contributing to hepatic insulin resistance.Good
- High plasma FFA concentrations impair muscle glycogen synthase (GS) activity, but this impairment occurs late (after 4-6 hours) and is associated with increased glucose-6-phosphate levels.Good
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