Effect of theophylline on substrate metabolism during exercise.
We tested the hypothesis that adenosine is involved in regulating substrate metabolism during exercise. Seven trained cyclists were studied during 30 minutes of exercise at approximately 75% maximal oxygen uptake (VO2max). Lipid metabolism was evaluated by infusing [2H5]glycerol and [1-13C]palmitate, and glucose kinetics were evaluated by infusing [6,6-2H]glucose. Fat and carbohydrate oxidation were also measured by indirect calorimetry. The same subjects performed two identical exercise tests, but in one trial theophylline, a potent adenosine receptor antagonist, was infused for 1 hour before and throughout exercise. Theophylline did not increase whole-body lipolysis (glycerol rate of appearance [Ra]) or free fatty acid (FFA) release during exercise, but fat oxidation was lower than control values (9.5 +/- 3.0 v 18.0 +/- 4.2 micromol x min(-1) x kg(-1), P < .01). Glucose Ra was not affected by theophylline infusion, but glucose uptake was lower (31.6 +/- 4.1 v 40.4 +/- 5.0 micromol x min(-1) x kg(-1), P < .05) and glucose concentration was higher (6.4 +/- 0.6 v 5.8 +/- 0.4 mmol/L, P < .05) than in the control trial. Total carbohydrate oxidation (302.3 +/- 26.2 v 265.5 +/- 11.7 micromol x min(-1) x kg(-1), P < .06), estimated muscle glycogenolysis (270.7 +/- 23.1 v 225.1 +/- 9.7 micromol x min(-1) x kg(-1), P < .05), and plasma lactate concentration (7.9 +/- 1.6 v 5.9 +/- 1.1 mmol/L, P < .001) were also higher during the theophylline trial. These data suggest that adenosine may play a role in stimulating glucose uptake and restraining glycogenolysis but not in limiting lipolysis during exercise.
Raguso
C A
CA
Metabolism Unit, Shriners Burns Institute, Galveston, TX 77550, USA.
Coggan
A R
AR
Sidossis
L S
LS
Gastaldelli
A
A
Wolfe
R R
RR
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002395:Catecholamines / Q000097:blood; D004734:Energy Metabolism; D015444:Exercise / Q000502:physiology*; D005260:Female; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism; D005990:Glycerol / Q000008:administration & dosage / Q000097:blood; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D009132:Muscles / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D013806:Theophylline / Q000494:pharmacology*
D001786:Blood Glucose; D002395:Catecholamines; D007328:Insulin; D010726:Phosphodiesterase Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D006003:Glycogen; D005934:Glucagon; D013806:Theophylline; D005947:Glucose; D005990:Glycerol