Insulin-Stimulated Muscle Glucose Uptake and Insulin Signaling in Lean and Obese Humans.
Level 4 - case-series / case-control
Cross-sectional comparative physiological study
PubMed 33382888 · doi:10.1210/clinem/dgaa919
What was done
Researchers investigated skeletal muscle insulin signaling in obesity across two protocols. Protocol 1 defined the linear range of insulin-stimulated systemic and leg glucose uptake in 14 obese and 14 nonobese volunteers using a 2-step insulin clamp. Protocol 2 evaluated 16 nonobese and 25 obese male and female volunteers (matched for fitness) using a 1-step hyperinsulinemic-euglycemic clamp combined with muscle biopsies to measure insulin-stimulated glucose disposal (Si), Akt and AS160 phosphorylation, and total muscle GLUT4 protein levels.
What was found
In Protocol 2, insulin-stimulated glucose disposal was reduced by > 60% in the obese group compared to nonobese controls (P < 0.0001). Phosphorylation of Akt and its downstream effector AS160 did not differ between the nonobese and obese groups. The increase in Akt2 phosphorylation in response to insulin positively correlated with Si in both nonobese (r = 0.53, P = 0.03) and obese (r = 0.55, P = 0.01) participants. Total muscle GLUT4 protein was 17% lower in the obese group (P < 0.05).
Why it matters
These findings suggest that skeletal muscle insulin resistance in human obesity is not caused by impaired Akt/AS160 signaling, indicating that models of acute lipotoxicity may not reflect the actual pathophysiology of obesity.
Limits
The study is limited by a relatively small sample size across two separate cohorts and a cross-sectional design that cannot determine causality. The abstract does not indicate whether participants overlapped between protocols, nor does it report downstream GLUT4 vesicle translocation dynamics.
Cited by
- supports Skeletal muscle is the primary site where the human body clears glucose from the bloodstream.