Suppression of systemic, intramuscular, and subcutaneous adipose tissue lipolysis by insulin in humans

In addition to sc and visceral fat deposits, muscle has been shown to conta in relevant amounts of lipids whose breakdown is subject to hormonal regula tion. The aim of the present study was to determine insulin dose-response c haracteristics of systemic, sc adipose tissue and muscle lipolysis in human s. We used a combination of isotopic (primed continuous infusion of [d(5)]g lycerol) and microdialysis techniques (catheters placed in the anterior tib ial muscle and sc abdominal adipose tissue) during a three-step hyperinsuli nemic-euglycemic clamp (insulin infusion, 0.1, 0.25, 1.0 mU/kg.min) in 13 l ean, healthy volunteers. The glycerol rate of appearance was used as the in dex for systemic lipolysis; interstitial glycerol concentrations were used as the index for muscle and sc adipose tissue lipolysis. The insulin concen trations resulting in a half-maximal suppression (EC50) of systemic lipolys is, adipose tissue, and muscle lipolysis were 51, 68, and 44 pmol/L, respec tively (between one another, P < 0.001). For each compartment there were si gnificant correlations between the EC50 and the insulin sensitivity index f or glucose disposal (r > 0.67; P < 0.05). However, lipolysis (as percent of baseline) was similar during the first two insulin infusion steps, but was significantly lower in adipose (22 +/- 2%) than in muscle (53 +/- 4%; P < 0.001) during step 3. Although we have no direct measurement of interstitia l insulin concentrations, we conclude that based on the EC50 values, muscle is more sensitive with respect to the net effect of circulating insulin (t ransendothelial transport plus intracellular action) on lipolysis than sc a dipose tissue in terms of exerting its full suppression within the physiolo gical insulin range. This could be important in muscle for switching from p referential utilization of free fatty acids to glucose in the postprandial state. Inadequate suppression of im lipolysis resulting in excessive local availability of free fatty acids may represent a novel mechanism contributi ng to the pathogenesis of impaired glucose disposal, i.e, insulin resistanc e, in muscle.