Interstitial glucose concentration in insulin-resistant human skeletal muscle: influence of one bout of exercise and of local perfusion with insulin or vanadate

Techniques in human skeletal muscle research are by necessity predominantly 'descriptive'.Microdialysis has raised high expectations that it could meet the demand for a method that allows 'mechanistic' investigations to be performed in human skeletal muscle. In the present review, some views are given on how well the initial expectations on the use of the microdialysis technique in skeletal muscle have been fulfilled, and the areas in which additional work is needed in order to validate microdialysis as an important metabolic technique in this tissue. The microdialysis catheter has been equated to an artificial blood vessel, which is introduced into the tissue. By means of this 'vessel' the concentrations of compounds in the interstitial space can be monitored. The concentration of substances in the collected samples is dependent on the rate of perfusate flow. When perfusate flow is slow enough to allow complete equilibration between interstitial and perfusate fluids, the concentration in the perfusate is maximal and identical to the interstitial concentration. Microdialysis data may be influenced by changes in blood flow, especially in instances where the tissue diffusivity limits the recovery in vivo, i.e. when recovery in vitro is 100 %, whereas the recovery in vivo is less than 100 %. Microdialysis data indicate that a significant arterial-interstitial glucose concentration gradient exists in skeletal muscle but not in adipose tissue at rest. While the concentrations of glucose and lactate in the dialysate from skeletal muscle are close to the expected values, the glycerol values obtained for muscle are still puzzling. Ethanol added to the perfusate will be cleared by the tissue at a rate that is determined by the nutritive blood flow (the microdialysis ethanol technique). It is concluded that microdialysis of skeletal muscle has become an important technique for mechanistic studies in human metabolism and nutrition.

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The proteomic signature of insulin-resistant human skeletal muscle reveals increased glycolytic and decreased mitochondrial enzymes

Diabetologia ◽

10.1007/s00125-012-2456-x ◽

2012 ◽

Vol 55 (4) ◽

pp. 1114-1127 ◽

Cited By ~ 43

Author(s):

J. Giebelstein ◽

G. Poschmann ◽

K. Højlund ◽

W. Schechinger ◽

J. W. Dietrich ◽

...

Keyword(s):

Skeletal Muscle ◽

Human Skeletal Muscle ◽

Mitochondrial Enzymes ◽

Insulin Resistant

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Leucine and insulin activate p70 S6 kinase through different pathways in human skeletal muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2001.281.3.e466 ◽

2001 ◽

Vol 281 (3) ◽

pp. E466-E471 ◽

Cited By ~ 89

Author(s):

Jeffrey S. Greiwe ◽

Guim Kwon ◽

Michael L. McDaniel ◽

Clay F. Semenkovich

Keyword(s):

Skeletal Muscle ◽

Amino Acids ◽

Protein Synthesis ◽

Human Skeletal Muscle ◽

Vastus Lateralis ◽

S6 Kinase ◽

Signaling Mechanism ◽

Insulin Resistant ◽

Branched Chain ◽

Plasma Leucine

Amino acids and insulin have anabolic effects in skeletal muscle, but the mechanisms are poorly understood. To test the hypothesis that leucine and insulin stimulate translation initiation in human skeletal muscle by phosphorylating 70-kDa ribosomal protein S6 kinase (p70S6k), we infused healthy adults with leucine alone ( n = 6), insulin alone ( n= 6), or both leucine and insulin ( n = 6) for 2 h. p70S6k and protein kinase B (PKB) serine473phosphorylation were measured in vastus lateralis muscles. Plasma leucine increased from ∼116 to 343 μmol/l during the leucine-alone and leucine + insulin infusions. Plasma insulin increased to ∼400 pmol/l during the insulin-alone and leucine + insulin infusions and was unchanged during the leucine-alone infusion. Phosphorylation of p70S6k increased 4-fold in response to leucine alone, 8-fold in response to insulin alone, and 18-fold after the leucine + insulin infusion. Insulin-alone and leucine + insulin infusions increased PKB phosphorylation, but leucine alone had no effect. These results show that physiological concentrations of leucine and insulin activate a key mediator of protein synthesis in human skeletal muscle. They suggest that leucine stimulates protein synthesis through a nutrient signaling mechanism independent of insulin, raising the possibility that administration of branched-chain amino acids may improve protein synthesis in insulin-resistant states.

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