Suppression of systemic, intramuscular, and subcutaneous adipose tissue lipolysis by insulin in humans.
Level 4 - case-series / case-control
Uncontrolled physiological intervention study in a single group of healthy human subjects
PubMed 11061533 · doi:10.1210/jcem.85.10.6898
What was done
Thirteen lean, healthy volunteers underwent a three-step hyperinsulinemic-euglycemic clamp (insulin infusion rates of 0.1, 0.25, and 1.0 mU/kg·min). Systemic lipolysis was determined using primed continuous infusion of [d5]glycerol to measure glycerol rate of appearance. Microdialysis catheters placed in the anterior tibial muscle and subcutaneous abdominal adipose tissue measured interstitial glycerol concentrations as indices of compartment-specific lipolysis and insulin dose-response characteristics.
What was found
The insulin concentration yielding half-maximal suppression (EC50) was 51 pmol/L for systemic lipolysis, 68 pmol/L for subcutaneous adipose tissue lipolysis, and 44 pmol/L for muscle lipolysis (P < 0.001 between compartments). EC50 in each compartment significantly correlated with the insulin sensitivity index for glucose disposal (r > 0.67; P < 0.05). Percent suppression of lipolysis from baseline was comparable during the first two insulin steps, but during step 3 was significantly greater in adipose tissue (residual lipolysis: 22 ± 2% of baseline) than in muscle (53 ± 4% of baseline; P < 0.001).
Why it matters
The study shows that intramuscular lipolysis is more sensitive to suppression by low physiological insulin levels than subcutaneous adipose tissue, although it reaches a higher plateau of residual lipolysis at higher insulin concentrations. This clarifies tissue-specific lipid turnover mechanisms involved in switching fuel utilization from fatty acids to glucose.
Limits
The sample size was small (n = 13) and restricted to lean, healthy volunteers without comparison to insulin-resistant cohorts. Interstitial insulin concentrations were not directly measured, and visceral adipose tissue was not evaluated.
Cited by
- supports Adipose tissue is highly sensitive to insulin, such that subtle amounts of insulin dramatically blunt fat breakdown and lipolysis.