The relation between increased availability of nonesterified fatty acids (NEFA) and impaired muscle glucose disposal is well established for insulin resistant states. Increased lipolysis in subcutaneous and visceral adipose tissue is commonly assumed to be the source of these NEFAs [1,2]. In addition to the well-known fat depots, however, muscle has been identified as tissue containing relevant amounts of lipids. These were shown to be located not only extramyocellularly but also intramyocellularly [2±4]. Moreover, a statistically significant correlation between the intramyocellular lipid content (by magnetic resonance spectroscopy) and insulin resistance (decreased metabolic clearance rate during a hyperinsulinaemic euglycaemic clamp) in normal glucose tolerant subjects was recently shown indicating an important role of muscular lipids for glucose homeostasis Diabetologia (1999) Abstract Aims/hypothesis. Both patients with Type II (non-insulin-dependent) diabetes mellitus and normoglycaemic, insulin resistant subjects were shown to have an increased lipid content in skeletal muscle, which correlates negatively with insulin sensitivity. Recently, it was shown that during a hyperinsulinaemic euglycaemic clamp interstitial glycerol was reduced not only in adipose tissue but also in skeletal muscle. To assess whether lipolysis of muscular lipids is also regulated by low physiological concentrations of insulin, we used the microdialysis technique in combination with a 3-step hyperinsulinaemic glucose clamp. Methods. Nineteen lean, healthy subjects (12 m/7 f) underwent a glucose clamp with various doses of insulin (GC I = 0.1, GC II = 0.25 and GC III = 1.0mUḱ g ±1´m in ±1 ). Two double lumen microdialysis catheters each were inserted in the paraumbilical subcutaneous adipose tissue and in skeletal muscle (tibialis anterior) to measure interstitial glycerol concentration (index of lipolysis) and ethanol outflow (index of tissue flow).Results. During the different steps of the glucose clamp, glycerol in adipose 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 reduced at GC III. Tissue flow was higher in the skeletal muscle and remained unchanged in both compartments throughout the experiment. Conclusion/interpretation. This study confirms the presence of glycerol release in skeletal muscle. Lipolysis in skeletal muscle and adipose tissue are suppressed similarly by minute and physiological increases in insulin but differently by supraphysiological increases. Inadequate suppression of intramuscular lipolysis resulting in increased availability of nonesterified fatty acids, could represent a potential mechanism involved in the pathogenesis of impaired glucose disposal, i. e. insulin resistance, in muscle. [Diabetologia (1999

Frequency‐selective chemical shift magnetic resonance (MR) imaging was applied on the calf musculature and the abdomen of a patient with acquired generalized lipoatrophy (AGL; Lawrence syndrome), a very rare syndrome affecting selectively several types of adipose tissue accompanied by alterations in glucose and energy metabolism. In addition, 1H‐MRS was used for assessment of intra‐ (IMCL) and extramyocellular lipid stores (EMCL) in the skeletal musculature of the calf. Results from the AGL patient were compared with an age‐matched group of five healthy volunteers. Fat‐selective imaging of the calf revealed a total lack of subcutaneous adipose tissue. No EMCL signal was found in the spectra from the soleus muscle of the AGL patient. IMCL signals were present in the spectra but were clearly lower than in the controls (14% of normal value in the soleus muscle). In abdominal images, subcutaneous fat signal was not detectable, as in the calf, but nearly normal conditions were shown for visceral adipose tissue between abdominal organs. Fat‐selective images showed the liver with high signal intensity, indicating hepatic steatosis combined with hepatosplenomegaly. Modern chemical shift‐selective MR imaging and localized spectroscopy allow a noninvasive and quantitative assessment of tissue composition in patients with disorders of carbohydrate and lipid metabolism. J. Magn. Reson. Imaging 2000;12:306–310. © 2000 Wiley‐Liss, Inc.

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In addition to sc and visceral fat deposits, muscle has been shown to contain relevant amounts of lipids whose breakdown is subject to hormonal regulation. The aim of the present study was to determine insulin dose-response characteristics of systemic, sc adipose tissue and muscle lipolysis in humans. We used a combination of isotopic (primed continuous infusion of [d5]glycerol) and microdialysis techniques (catheters placed in the anterior tibial muscle and sc abdominal adipose tissue) during a three-step hyperinsulinemic-euglycemic clamp (insulin infusion, 0.1, 0.25, 1.0 mU/kg x min) in 13 lean, healthy volunteers. The glycerol rate of appearance was used as the index for systemic lipolysis; interstitial glycerol concentrations were used as the index for muscle and sc adipose tissue lipolysis. The insulin concentrations resulting in a half-maximal suppression (EC50) of systemic lipolysis, adipose tissue, and muscle lipolysis were 51, 68, and 44 pmol/L, respectively (between one another, P < 0.001). For each compartment there were significant correlations between the EC50 and the insulin sensitivity index for 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 interstitial insulin concentrations, we conclude that based on the EC50 values, muscle is more sensitive with respect to the net effect of circulating insulin (transendothelial transport plus intracellular action) on lipolysis than sc adipose tissue in terms of exerting its full suppression within the physiological insulin range. This could be important in muscle for switching from preferential 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 contributing to the pathogenesis of impaired glucose disposal, i.e. insulin resistance, in muscle.