Biomedical subjects

Wayne T Willis

Publications and source records attributed to Wayne T Willis.

4 recordsLinked to original sources

PubMed2005

Fuel oxidation during human walking.

Human adults walk at a characteristic speed, but the mechanisms responsible for this ubiquitous and reproducible behavior remain unknown. In this study, preferred walking speed (PWS) was 4.7 +/- 0.1 km h -1 in 12 overnight-fasted adults, mean age 30.0 +/- 2.6 years. Indirect calorimetry was used to measure fuel oxidation during level treadmill walking from 3.2 to 7.2 km h -1 progressively increased at increments of 0.8 km h -1 and 10.0-min intervals. Corroborating many previous reports, the O2 cost of transport (mL O2 kg -1 km -1 ) was numerically lowest at 4.8 km h -1 , near PWS, but was not significantly different than 5.6 km h -1 . The impact of walking speed on the fuel selection of skeletal muscle was much more dramatic. At speeds less than or equal to PWS, muscle carbohydrate (CHO) oxidation rates were quite low, in the range that could be matched by gluconeogenesis. Above 4.8 km h -1 , CHO oxidation rate increased abruptly and tracked the perception of effort (RPE). Stepwise linear regression revealed that CHO oxidation explained 70% of the variance in RPE, and speed provided an additional 4%. In contrast, the other variables included in the analysis, fat oxidation rate, heart rate, and O2 cost of transport, contributed no additional explained variance in RPE. We conclude that PWS is just below a threshold speed, above which CHO oxidation abruptly increases. The central nervous system may be guided by the perception of effort in selecting a PWS that minimizes dependence on CHO oxidation. We further conclude that skeletal muscle metabolic control is an important factor to be taken into account by the central nervous system motor control of human locomotion.

Adenosine Triphosphate↗

PubMed2004

Epidural spinal-cord stimulation facilitates recovery of functional walking following incomplete spinal-cord injury.

We investigated a novel treatment paradigm for developing functional ambulation in wheelchair-dependent individuals with chronic, incomplete spinal-cord injury. By coordinating epidural stimulation of the dorsal structures of the spinal cord with partial weight bearing treadmill therapy, we observed improvement in treadmill and over-ground ambulation in an individual with chronic incomplete tetraplegia. The application of partial weight-bearing therapy alone was not sufficient to achieve functional ambulation over ground, though treadmill ambulation improved significantly. Combining epidural spinal-cord stimulation (ESCS, T10-T12 vertebral levels) with partial weight-bearing therapy resulted in further improvement during treadmill ambulation. Moreover, the combination of therapies facilitated the transfer of the learned gait into over ground ambulation. Performance improvements were elicited by applying continuous, charge-balanced, monophasic pulse trains at a frequency of 40-60 Hz, a pulse duration of 800 micros, and an amplitude determined by the midpoint (50%) between the sensory and motor threshold values. The participant initially reported a reduction in sense of effort for over ground walking from 8/10 to 3/10 (Borg scale), and was able to double his walking speed. After several weeks of over ground training, he reached maximum walking speeds of 0.35 m/s, and was able to ambulate over 325 m. We propose that ESCS facilitated locomotor recovery in this patient by augmenting the use-dependent plasticity created by partial weight bearing therapy. Confirmation of these promising results in a controlled study of groups of spinal-cord-injured subjects is warranted.

Adaptation, Physiological↗

PubMed2003

Pyruvate and citric acid cycle carbon requirements in isolated skeletal muscle mitochondria.

Carbohydrate depletion precipitates fatigue in skeletal muscle, but, because pyruvate provides both acetyl-CoA for mainline oxidation and anaplerotic carbon to the citric acid cycle (CAC), the mechanism remains obscure. Thus pyruvate and CAC kinetic parameters were independently quantified in mitochondria isolated from rat mixed skeletal muscle. Mitochondrial oxygen consumption rate (Jo) was measured polarographically while either pyruvate or malate was added stepwise in the presence of a saturating concentration of the other substrate. These substrate titrations were carried out across a physiological range of fixed extramitochondrial ATP free energy states (DeltaGP), established with a creatine kinase energy clamp, and also at saturating [ADP]. The apparent Km,malate for mitochondrial Jo ranged from 21 to 32 microM, and the apparent Km,pyruvate ranged from 12 to 26 microM, with both substrate Km values increasing as DeltaGP declined. Vmax for both substrates also increased as DeltaGP fell, reflecting thermodynamic control of Jo. Reported in vivo skeletal muscle [malate] are >10-fold greater than the Km,malate determined in this study. In marked contrast, the K(m,pyruvate) determined is near the [pyruvate] reported in muscle approaching exhaustion associated with glycogen depletion. When data were evaluated in the context of a linear thermodynamic force-flow (DeltaGP-Jo) relationship, the DeltaGP-Jo slope was essentially insensitive to changes in [malate] in the range observed in vivo but decreased markedly with declining [pyruvate] across the physiological range. Mitochondrial respiration is particularly sensitive to variations in [pyruvate] in the physiological range. In contrast, physiological [malate] exerts very little, if any, influence on mitochondrial pyruvate oxidation measured in vitro.

Animals↗

PubMed2002

Diets enriched in sucrose or fat increase gluconeogenesis and G-6-Pase but not basal glucose production in rats.

High-fat (HFD) and high-sucrose diets (HSD) reduce insulin suppression of glucose production in vivo, increase the capacity for gluconeogenesis in vitro, and increase glucose-6-phosphatase (G-6-Pase) activity in whole cell homogenates. The present study examined the effects of HSD and HFD on in vivo gluconeogenesis, the catalytic and glucose-6-phosphate translocase subunits of G-6-Pase, glucokinase (GK) translocation, and glucose cycling. Rats were fed a high-starch control diet (STD; 68% cornstarch), HSD (68% sucrose), or HFD (45% fat) for 7-13 days. The ratio of 3H in C6:C2 of glucose after 3H2O injection into 6- to 8-h-fasted rats was significantly increased in HSD (0.68 +/- 0.07) and HFD (0.71 +/- 0.08) vs. STD (0.40 +/- 0.10). G-6-Pase activity was significantly higher in HSD and HFD vs. STD in both intact and disrupted liver microsomes. HSD and HFD significantly increased the amount of the p36 catalytic subunit protein, whereas the p46 glucose-6-phosphate translocase protein was increased in HSD only. Despite increased nonglycerol gluconeogenesis and increased G-6-Pase, basal glucose and insulin levels as well as glucose production were not significantly different among groups. Hepatocyte cell suspensions were used to ascertain whether diet-induced adaptations in glucose phosphorylation and GK might serve to compensate for upregulation of G-6-Pase. Tracer-estimated glucose phosphorylation and glucose cycling (glucose <--> glucose 6-phosphate) were significantly higher in cells isolated from HSD only. After incubation with either 5 or 20 mM glucose and no insulin, GK activity (nmol. mg protein(-1). min(-1)) in digitonin-treated eluates (translocated GK) was significantly higher in HSD (32 +/- 4 and 146 +/- 6) vs. HFD (4 +/- 1 and 83 +/- 10) and STD (9 +/- 2 and 87 +/- 9). Thus short-term, chronic exposure to HSD and HFD increase in vivo gluconeogenesis and the G-6-Pase catalytic subunit. Exposure to HSD diet also leads to adaptations in glucose phosphorylation and GK translocation.

Animals↗