Thorell · The American journal of physiology 1999 · within-subject crossover physiological study · n=9

Exercise and insulin cause GLUT-4 translocation in human skeletal muscle.

Cited 191 times in the scientific literature.

Level 3 - non-randomized controlled study

Non-randomized within-subject crossover physiological study in healthy humans

PubMed 10516134 · doi:10.1152/ajpendo.1999.277.4.E733 · record verified 2026-08-29

What was done

Nine healthy volunteers were tested on two separate days. On one day, vastus lateralis muscle biopsies were obtained before and after a 2-hour euglycemic-hyperinsulinemic clamp (0.8 mU·kg⁻¹·min⁻¹). On the other day, participants completed 60 minutes of exercise at 70% VO₂ max, underwent a biopsy, and then underwent the identical clamp and biopsy protocol. Plasma membrane GLUT-4 content, Akt phosphorylation, and glucose infusion rates were measured.

What was found

Glucose infusion rates were significantly higher during the post-exercise clamp than during insulin alone for intervals 0–30 min, 30–60 min, and 60–90 min, but not during the final 30 min. Compared to rest, plasma membrane GLUT-4 content increased significantly with insulin alone (32%), exercise alone (35%), and exercise plus insulin (44%). Akt phosphorylation increased by 640% above rest with insulin, 280% with exercise, and 1,000% with exercise plus insulin.

Why it matters

This study directly confirms in human skeletal muscle that physiological hyperinsulinemia and moderate exercise activate Akt and mobilize GLUT-4 to the cell membrane, validating mechanisms previously demonstrated mainly in rodents.

Limits

The sample size was very small (n = 9) and included only healthy volunteers, precluding direct generalization to clinical populations such as individuals with type 2 diabetes. The abstract does not report randomization of trial day order or provide exact variance and confidence intervals.

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