Thomas W. Balon

Prior exercise potentiates the thermic effect of a carbohydrate load

It is unclear whether dietary-induced thermogenesis (DIT) is increased after exercise. To test this possibility, six healthy volunteers, male and female, exercised for 45 minutes at 70% of maximal aerobic capacity (VO2 max) in the morning after an overnight fast. Two hours after the end of the exercise, by which time VO2 had returned to near baseline levels, subjects ingested a 100-g glucose load. Blood samples and respiratory gas exchange data were collected over the next three hours. On a separate day on which the subjects did not exercise, the test procedure was repeated. Glucose tolerance and the insulin response to the glucose load were not significantly different between the two trials; however, VO2 increased by 15.5% over baseline on the exercise day, compared with only 8.9% when exercise was not performed. The net increase in energy expenditure for the three-hour period following glucose ingestion was 15 kcal/180 min greater on the exercise than on the control day, with increases upwards of 20 kcal/180 min in several individuals. No correlation was found between the magnitude of exercise-enhanced DIT and VO2 max, suggesting that this effect is independent of the state of training. The results indicate that the thermic effect of exogenous carbohydrate can be potentiated by prior exercise.

Redox regulation of skeletal muscle glucose transport.

Although the control of carbohydrate metabolism may be regulated by numerous factors, the redox state of the cell is of primary importance. The redox state may be influenced by a number of different factors, including different reactive oxygen species (ROS) and reactive nitrogen species (RNS) collectively, called reactive oxygen/nitrogen species (RONS). This review attempts to summarize the importance of redox regulation in relation to glucose transport and regulation of carbohydrate metabolism in skeletal muscle. In addition, prior studies implicating the role of different RONS in the control of glucose transport in skeletal muscle will be presented. Finally, the possible involvement of the cGMP, p21ras, and mean arterial pressure (MAP) kinase signal transduction cascades, which have been implicated with redox-sensitive alterations in glucose transport, will also be discussed.

Nutrient Excess and AMPK Downregulation in Incubated Skeletal Muscle and Muscle of Glucose Infused Rats

We have previously shown that incubation for 1h with excess glucose or leucine causes insulin resistance in rat extensor digitorum longus (EDL) muscle by inhibiting AMP-activated protein kinase (AMPK). To examine the events that precede and follow these changes, studies were performed in rat EDL incubated with elevated levels of glucose or leucine for 30min-2h. Incubation in high glucose (25mM) or leucine (100μM) significantly diminished AMPK activity by 50% within 30min, with further decreases occurring at 1 and 2h. The initial decrease in activity at 30min coincided with a significant increase in muscle glycogen. The subsequent decreases at 1h were accompanied by phosphorylation of αAMPK at Ser485/491, and at 2h by decreased SIRT1 expression and increased PP2A activity, all of which have previously been shown to diminish AMPK activity. Glucose infusion in vivo, which caused several fold increases in plasma glucose and insulin, produced similar changes but with different timing. Thus, the initial decrease in AMPK activity observed at 3h was associated with changes in Ser485/491 phosphorylation and SIRT1 expression and increased PP2A activity was a later event. These findings suggest that both ex vivo and in vivo, multiple factors contribute to fuel-induced decreases in AMPK activity in skeletal muscle and the insulin resistance that accompanies it.

Insulin and exercise stimulate muscle alpha-aminoisobutyric acid transport by a Na+K+-ATPase independent pathway

Sodium ions are required for the active transport of amino acids such as alpha-aminoisobutyric acid (AIB) into skeletal muscle. To examine the role of Na+-K+-ATPase in this phenomenon, studies were carried out using the isolated perfused rat hindquarter preparation. Perfusion for 30 min with ouabain at a dose sufficient to inhibit the Na+-K+ pump (10(-4) M) inhibited the basal rate of AIB uptake in all muscles studied by up to 80%. However, it failed to inhibit the stimulation of AIB uptake, either by insulin (200 microU/ml) or electrically-induced muscle contractions. The increase in K+ release by the hindquarter in the presence of ouabain was the same under all conditions suggesting comparable inhibition of the Na+-K+ pump. These studies suggest that the basal, but not insulin or exercise-stimulated AIB transport into muscle is acutely dependent on a functional Na+-K+ pump. They also suggest that stimulated and basal uptake of AIB involve different mechanisms.