Hormonal
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.
High levels of free fatty acids in your blood can block insulin from helping your muscles take up glucose. This happens through two main pathways: it stops your muscles from storing glucose as glycogen and reduces the amount of glucose you burn for energy. This effect is dose-dependent, meaning higher fat levels lead to greater insulin resistance. For healthy individuals, this suggests that managing fat metabolism is crucial for maintaining insulin sensitivity.
We concluded that fatty acids caused a dose-dependent inhibition of insulin-stimulated glucose uptake (by decreasing glycogen synthesis and CHO oxidation)... and that FFA and/or glycerol increased insulin-suppressed hepatic glucose output and thus caused insulin resistance at the peripheral and the hepatic level.
Why this rating
Controlled human clinical trial with rigorous measurement of metabolic pathways.
Source
Mechanisms of fatty acid-induced inhibition of glucose uptake.
G Boden et al. · Journal of Clinical Investigation · 1994
DOI 10.1172/jci117252
More from this paper
- 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
- 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.Good
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