Insulin-mediated skeletal muscle vasodilation contributes to both insulin sensitivity and responsiveness in lean humans.
Level 3 - non-randomized controlled study
Non-randomized within-subject controlled physiological interventional study.
PubMed 7635973 · doi:10.1172/JCI118124
What was done
Researchers measured leg glucose uptake in lean humans during euglycemic hyperinsulinemic clamps at two insulin doses: 40 mU/m² per min (n = 6) and 120 mU/m² per min (n = 15). To blunt insulin-mediated vasodilation, NG-monomethyl-L-arginine (L-NMMA) was infused directly into the femoral artery during hyperinsulinemia, comparing leg blood flow and glucose uptake with and without local nitric oxide synthase blockade.
What was found
During the higher-dose insulin study, hyperinsulinemia increased basal leg blood flow from 0.24 ± 0.02 to 0.45 ± 0.05 L/min (P < 0.0001). L-NMMA infusion reduced leg glucose uptake by 21%, from 114 ± 18 mg/min to 85 ± 13 mg/min (P < 0.001). Whole-body insulin-stimulated glucose uptake correlated with flow-dependent glucose uptake (r = 0.57, P = 0.02). Similar findings were reported for the lower-dose insulin infusion, although specific numerical values were not stated in the abstract.
Why it matters
This study provides physiological evidence in humans that insulin-mediated vasodilation directly contributes to skeletal muscle glucose disposal, establishing muscle perfusion as an active determinant of insulin sensitivity and responsiveness.
Limits
The sample size was small (n = 21 across two dose groups), and the study only evaluated healthy lean individuals. The protocol relied on acute pharmacological blockade during non-physiological hyperinsulinemic clamps. Exact numerical values for the low-dose cohort were not reported in the abstract.
Cited by
- supports Muscle glucose uptake partially depends on nitric oxide-mediated vasodilation to deliver glucose, and inhibiting this mechanism can cause insulin resistance.