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

Abstract

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

Evidence for a Major Role of Skeletal Muscle Lipolysis in the Regulation of Lipid Oxidation During Caloric Restriction In Vivo

“…Skeletal muscle blood flow was not changed by insulin infusion before dieting, a finding which is in accordance with previous studies (14,15). Interstitial muscle glycerol levels were decreased after insulin infusion in agreement with earlier findings (7,14). However, the rate of glycerol release was not influenced by insulin.…”

“…Furthermore, several groups have demonstrated marked lipolytic activity in human skeletal muscle (5)(6)(7), generating glycerol and free fatty acids (FFAs) from TGs by hydrolysis. It appears that lipolysis in skeletal muscle is regulated in a different manner than in adipose tissue.…”

Intranasal application of the melanocortin 4 receptor agonist MSH/ACTH(4–10) in humans causes lipolysis in white adipose tissue

“…It is known that intramuscular fat depots could have an important role in energy homeostasis, while also SM might be differently affected by lipomotor signals than adipose tissue. [14][15][16][17] Neither baseline sympathetic neuronal outflow to the muscle vascular bed nor glycerol release within the muscle was significantly affected by MSH/ACTH(4-10) under baseline conditions. However, our negative findings in the forearm muscle do not necessarily apply to all SM in general, as there is a marked heterogeneity between different SM groups regarding lipolysis.…”

Heterogeneity in limb fatty acid kinetics in type 2 diabetes

“…Furthermore, heterogeneity in adipose tissue [39] and skeletal muscle [16] lipolysis has been reported. In addition, skeletal muscle and adipose tissue lipolysis can respond differently to insulin [40][41][42][43], also in relation to the insulin level [44,45]. Taken together, these factors hamper a clear interpretation of palmitate release in the arm and leg of healthy individuals and diabetic patients.…”