Interleukin-6 mediates exercise-induced increase in insulin sensitivity in mice.
Level 5 - mechanism / opinion, no new human data
Preclinical animal model (non-human experiment)
PubMed 22523382 · doi:10.1113/expphysiol.2012.065508
What was done
Researchers evaluated the acute and chronic roles of interleukin-6 (IL-6) in exercise-mediated glucose regulation using IL-6-deficient (IL-6-/-) and wild-type control mice. Acute glucose uptake after a single exercise bout was evaluated via [3H]2-deoxyglucose tracer clearance and muscle uptake in the extensor digitorum longus. In a chronic study, wild-type and IL-6-/- mice were placed on a high-fat diet with or without voluntary running-wheel access to assess changes in insulin sensitivity (via insulin tolerance test AUC), serum retinol-binding protein-4 (RBP-4) levels, food intake, body weight, and body composition.
What was found
After acute exercise, serum tracer disappearance did not differ between IL-6-/- and wild-type mice (13565 ± 426 vs. 14343 ± 1309 d.p.m. min ml^-1, P = 0.5), but glucose uptake in extensor digitorum longus muscle was significantly lower in IL-6-/- mice (398 ± 44 vs. 657 ± 41 nmol g^-1 min^-1, P < 0.01). Under high-fat feeding, sedentary mice of both genotypes experienced a ~20% increase in insulin tolerance test glucose AUC (P < 0.05) and a 30% increase in serum RBP-4 (P < 0.01). Running wheel access protected wild-type mice from high-fat-diet-induced insulin resistance, but IL-6-/- runners gained no significant protection, maintaining similar insulin resistance to sedentary IL-6-/- controls (AUC 312 ± 14 vs. 340 ± 22 mmol min l^-1, P = 0.4) and showing a 14% increase in serum RBP-4 (P < 0.01).
Why it matters
The findings demonstrate that endogenous IL-6 is required for voluntary exercise to prevent high-fat-diet-induced insulin resistance in mice, establishing muscle-derived IL-6 as a key mediator of long-term metabolic adaptations to exercise.
Limits
This is an animal study in knockout mice, limiting direct translation to human physiology. Sample sizes for each experimental group were not reported in the abstract.
Cited by
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