Regulation of Glucose Utilization During the Inhibition of Fatty Acid Oxidation in Rat Myocytes

Abstract

The study of the regulation of glucose utilization by inhibition of fatty acid oxidation is greatly enhanced by the availability of specific inhibitors of fatty acid oxidation. This study examines the regulation of cardiac glucose utilization by inhibition of fatty acid oxidation at different sites. The effects of Etomoxir and 4-bromocrotonic acid (4-BCA) on the oxidation of [1-14C]palmitate, [1-14C]-octanoate and [U-14C]glucose were studied in isolated rat myocytes. Fifty percent inhibition of palmitate oxidation was achieved at 8 microM Etomoxir and 40 microM 4-BCA. Octanoate oxidation was inhibited only by 4-BCA. In contrast to their effect on palmitate oxidation, these inhibitors significantly stimulated the oxidation of glucose in a concentration-dependent manner. Moreover, the oxidation of [2-14C]pyruvate was increased two-fold by these compounds. The rate of utilization of [U-14C]-2-deoxyglucose was also stimulated 2-3 times by these inhibitors. These studies suggest that the stimulation of glucose utilization via the inhibition of fatty acid oxidation may be mediated through the stimulation of both glucose transport and the oxidation of pyruvate by the pyruvate dehydrogenase complex.

Reduced Induction of Carbohydrate Utilization by Inhibition of Fatty Acid Oxidation in Myocytes from Diabetic Animals

“…However, the stimulation of pyruvate oxidation was much less sensitive to etomoxir in myocytes from diabetic rats compared to its effect in normal my ocytes. In normal myocytes, pyruvate oxidation was increased twofold by 50 iM etomoxir (Abdel-aleem et al '1994). These results are consistent with the studies of Denton et al who demonstrated a significant difference in the PDH sensitivity to substrate activation in mitochondria prepared from diabetic and normal rats (Denton, Randle, Bridges and Cooper 1975).…”

Fatty acid metabolism during maturation affects glucose uptake and is essential to oocyte competence

“…Furthermore, overexpression of glucose transporter Slc2a1 in mouse cardiac tissue increases glucose uptake and oxidation while decreasing FAO, despite a high supply of fatty acids (Yan et al 2009). A relationship between FAO and glucose consumption and oxidation has also been reported in rat hepatocytes (Berry et al 1993), rat myocytes (Abdel-aleem et al 1994), rat skeletal muscle (Kaushik et al 2001), and rat (Saddik et al 1993, Lavrentyev et al 2004) and mouse cardiac tissues (Campbell et al 2002).…”

In Skeletal Muscle, Glucose Storage and Oxidation Are Differentially Impaired by the IR1152 Mutant Receptor

“…Glucose Oxidation and Pyruvate Dehydrogenase Activity-Glucose oxidation was determined by a modification of the method of Lowe and coworkers (26). Briefly, for these experiments, cells were grown in 50-ml flasks and preincubated in serum-free DMEM for 18 h before the experiment.…”