Interstitial fluid concentrations of glycerol, glucose, and amino acids in human quadricep muscle and adipose tissue. Evidence for significant lipolysis in skeletal muscle.

Abstract

To determine the relationship between circulating metabolic fuels and their local concentrations in peripheral tissues we measured glycerol, glucose, and amino acids by microdialysis in muscle and adipose interstitium of 10 fasted, nonobese human subjects during (a) baseline, (b) euglycemic hyperinsulinemia (3 mU/kg per min for 3 h) and, (c) local norepinephrine reuptake blockade (NOR). At baseline, interstitial glycerol was strikingly higher (P < 0.0001) in muscle (3710 jLM) and adipose tissue (2760 ,uM) compared with plasma (87 ,LM), whereas interstitial glucose (muscle 3.3, fat 3.6 mM) was lower (P < 0.01) than plasma levels (4.8 mM). Taurine, glutamine, and alanine levels were higher in muscle than in adipose or plasma (P < 0.05). Euglycemic hyperinsulinemia did not affect interstitial glucose, but induced a fall in plasma glycerol and amino acids paralleled by similar changes in the interstitium of both tissues. Local NOR provoked a fivefold increase in glycerol (P < 0.001) and twofold increase in norepinephrine (P < 0.01) in both muscle and adipose tissues. To conclude, interstitial substrate levels in human skeletal muscle and adipose tissue differ substantially from those in the circulation and this disparity is most pronounced for glycerol which is raised in muscle as well as adipose tissue. In muscle, insulin suppressed and NOR increased interstitial glycerol concentrations. Our data suggest unexpectedly high rates of intramuscular lipolysis in humans that may play an important role in fuel metabolism. (J. Clin. Invest. 1995. 96:370-377.)

Abnormal myocardial kinetics of 123 I-heptadecanoic acid in subjects with impaired glucose tolerance

“…The existence of a VLDL receptor [36], highly abundant in the heart and capable of mediating uptake of apolipoprotein E-containing triglyceride-rich particles, fits well with this hypothesis. Furthermore, a recent study suggested that intramuscular lipolysis in the skeletal muscle may be unexpectedly high and regulate fuel metabolism [37]. In the present study S I and 2-h glucose determined in the IGT group correlated with the kinetic abnormalities of HDA, suggesting that insulin resistance per se or the underlying factors are directly responsible for the observed disturbances in fatty acid metabolism.…”

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

“…This observation was made previously during a standard 2-h (insulin infusion of 1 mU´kg ±1´m in ±1 ) [6,7] and also during a 3-h hyperinsulinaemic clamp using even higher insulin infusion rates (3 mU´kg ±1´m in ±1 ) [5]. There is no satisfactory explanation for this phenomenon.…”

“…Interstitial glycerol which is neither taken up nor metabolised to a major extent by adipose tissue and skeletal muscle is generally accepted as a qualitative index of hydrolysis of lipids [5±7]. Therefore, changes in dialysate glycerol reflect changes in tissue lipolysis [5,6].…”

Prostaglandin synthesis can be inhibited locally by infusion of NSAIDS through microdialysis catheters in human skeletal muscle

“…Microdialysis makes it possible to determine the local concentration of water-soluble substances, e.g., PGs. In addition, the microdialysis technique can be used to introduce substances locally into human tissue (3,9,13), although this technique is not widely used yet. In the present study the microdialysis method was used to infuse NSAIDs locally within the human skeletal muscles to produce a local block of PG formation.…”