Glucose and insulin-induced inhibition of fatty acid oxidation: the glucose-fatty acid cycle reversed.
In this study we have investigated a hypothesis that proposes the reverse of the so-called "glucose-fatty acid cycle, " i.e., that accelerated carbohydrate metabolism directly inhibits fatty acid oxidation. We studied normal volunteers in the basal state and during a hyperinsulinemic, hyperglycemic clamp (plasma insulin = 1,789 +/- 119 pmol/l, plasma glucose = 7.7 +/- 0.2 mmol/l). We quantified fat oxidation using indirect calorimetry and stable isotopes ([1-13C]oleate). Plasma oleate enrichment and free fatty acid (FFA) concentration were kept constant by means of infusion of lipids and heparin. Glucose oxidation increased from basal 6.2 +/- 0.8 to 22.3 +/- 1.4 mumol.kg-1.min-1 during the clamp (P < 0.01). Total (indirect calorimetry) and plasma fatty acid oxidation (isotopic determination) decreased from 2.6 +/- 0.2 to 0.4 +/- 0.3 (P < 0.01) and 2.2 +/- 0.2 to 1.4 +/- 0.1 mumol.kg-1.min-1 (P <0.05), respectively. We conclude that under the conditions of the present experiment, glucose and/or insulin directly inhibits fatty acid oxidation. Our findings suggest that, contrary to the prediction of the glucose-fatty acid cycle, the intracellular availability of glucose (rather than FFA) determines the nature of substrate oxidation in human subjects.
Sidossis
L S
LS
Metabolism Unit, Shriners Burns Institute, Galveston, Texas, USA.
Wolfe
R R
RR
D000328:Adult; D002153:Calorimetry, Indirect; D005227:Fatty Acids / Q000037:antagonists & inhibitors* / Q000097:blood*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects
D005227:Fatty Acids; D007328:Insulin; D005947:Glucose