Insulin sensitivity of protein and glucose metabolism in human forearm skeletal muscle.
Level 3 - non-randomized controlled study
Controlled non-randomized or unstated-randomization human physiological dose-response study.
PubMed 1469091 · doi:10.1172/JCI116124
What was done
Using the forearm perfusion technique in 35 human subjects, researchers infused insulin locally into the brachial artery for 150 minutes across five dosage rates: 0.00 (saline control), 0.01, 0.02, 0.035, and 0.05 mU/min per kg. These infusions elevated local forearm plasma insulin by approximately 0, 20, 35, 60, and 120 microU/ml. Systemic infusions of L-[ring-2,6-3H]phenylalanine and L-[1-14C]leucine were administered to quantify net forearm amino acid balance, rate of appearance (Ra, reflecting proteolysis), rate of disposal (Rd, reflecting protein synthesis), and forearm glucose uptake.
What was found
Forearm glucose uptake increased dose-dependently from 0.9 mumol/min per 100 ml forearm tissue in the saline control to 1.0, 1.8, 2.4, and 4.7 mumol/min per 100 ml across increasing insulin doses. In contrast, net balance of phenylalanine and leucine became significantly less negative than basal (P < 0.01 for each) at the lowest insulin infusion rate (0.01 mU/min per kg), with no greater suppression at higher doses. Phenylalanine and leucine Ra declined by approximately 38% and 40% with the lowest dose, while higher doses produced similar declines (26% to 42% for phenylalanine, 30% to 50% for leucine). Amino acid Rd did not change with insulin.
Why it matters
This study demonstrates that skeletal muscle proteolysis is more sensitive to insulin than glucose uptake, achieving near-maximal suppression at low physiological increments in plasma insulin.
Limits
The abstract does not state participant sex, age, health characteristics, or whether subjects were randomized across infusion doses. The protocol was limited to acute 150-minute local arterial infusions, which may not capture systemic or long-term metabolic adaptations.
Cited by
- supports Only a low concentration of insulin is required to inhibit muscle proteolysis.