Introduction
Most cells obtain their energy supply through oxidation of substrates and this increase further during conditions of increased energy consumption, i.e. during exercise. Previous studies have established the importance of the interregulation between glucose and fatty acids on substrate oxidation in skeletal muscle in vivo and in vitro. First, the glucose-fatty acid cycle by Randle et al. [1] showed that exogenous fatty acids could reduce glucose oxidation; second, hyperglycemia could in turn reduce fatty acid oxidation in skeletal muscle, designating the reverse Randle cycle [2], [3] and [4]. We have shown that glucose oxidation can be reduced by palmitate (PA) and glucose oxidation is increasing during conditions of increased glucose availability [5]. Despite these observations it is not clear if substrate oxidation is a dynamic process at higher levels of substrate availability, i.e. whether glucose inhibited lipid oxidation may increase again with increasing free fatty acid (FFA) concentration and vice versa. Cultured human myotubes represent a well-characterized in vitro model of skeletal muscle, which previously has been used to separate the contribution of intracellular and extracellular substrates on substrate oxidation [5], [6] and [7]. In the present study, we took advantage of this model to investigate lipid and glucose oxidation in human myotubes established from healthy, lean subjects, exposed to stepwise increased PA and glucose concentrations, in order to examine the impact of alterations in extracellular lipid and glucose concentrations on their own and the oxidation of each other.