Lipolysis in skeletal muscle is rapidly regulated by low physiological doses of insulin

Aims/hypothesis. Both patients with Type II (non-insulin-dependent) diabete s mellitus and normoglycaemic, insulin resistant subjects were shown to hav e an increased lipid content in skeletal muscle, which correlates negativel y with insulin sensitivity. Recently, it was shown that during a hyperinsul inaemic euglycaemic clamp interstitial glycerol was reduced not only in adi pose tissue but also in skeletal muscle. To assess whether lipolysis of mus cular lipids is also regulated by low physiological concentrations of insul in, we used the microdialysis technique in combination with a 3-step hyperi nsulinaemic glucose clamp. Methods. Nineteen lean, healthy subjects (12 m/7f) underwent a glucose clam p with various doses of insulin (GC I = 0.1, GC II = 0.25 and GC III = 1.0 mU.kg(-1).min(-1)). Two double lumen microdialysis catheters each were inse rted in the paraumbilical subcutaneous adipose tissue and in skeletal muscl e (tibialis anterior) to measure interstitial glycerol concentration (index of lipolysis) and ethanol outflow (index of tissue now). Results. During the different steps of the glucose clamp, glycerol in adipo se tissue was reduced to 81 +/- 7% (GC I), 55 +/- 8% (GC II) and 25 +/- 5% (GC III), respectively, of basal. In contrast, glycerol in skeletal muscle declined to 73 +/- 5% (GC I) and to 57 +/- 6% (GC II) but was not further r educed at GC III. Tissue flow was higher in the skeletal muscle and remaine d unchanged in both compartments throughout the experiment. Conclusion/interpretation. This study confirms the presence of glycerol rel ease in skeletal muscle. Lipolysis in skeletal muscle and adipose tissue ar e suppressed similarly by minute and physiological increases in insulin but differently by supraphysiological increases. Inadequate suppression of int ramuscular lipolysis resulting in increased availability of nonesterified f atty acids, could represent a potential mechanism involved in the pathogene sis of impaired glucose disposal, i.e. insulin resistance, in muscle.