Lipolysis in skeletal muscle is rapidly regulated by low physiological doses of insulin.
OBJECTIVE
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 = 1.0 mU x kg(-1) x min(-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.


CONCLUSIONS
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 non-esterified fatty acids, could represent a potential mechanism involved in the pathogenesis of impaired glucose disposal, i. e. insulin resistance, in muscle. [Diabetologia (1999) 42: 1171-1174]
Jacob
S
S
Department of Endocrinology and Metabolism, University of Tübingen, Germany.
Hauer
B
B
Becker
R
R
Artzner
S
S
Grauer
P
P
Löblein
K
K
Nielsen
M
M
Renn
W
W
Rett
K
K
Wahl
H G
HG
Stumvoll
M
M
Häring
H U
HU
D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose; D000431:Ethanol / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000097:blood / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D008066:Lipolysis / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D000431:Ethanol; D005990:Glycerol