Regulation of insulin signalling by exercise in skeletal muscle

Regular physical activity improves insulin action and is an effective therapy for the treatment and prevention of type 2 diabetes. However, little is known of the mechanisms by which exercise improves insulin action in muscle. These studies investigate the actions of a single bout of exercise and short-term endurance training on insulin signalling. Twenty-four hours following the completion of a single bout of endurance exercise insulin action improved, although greater enhancement of insulin action was demonstrated following the completion of endurance training, implying that cumulative bouts of exercise substantially increase insulin action above that seen from the residual effects of an acute bout of prior exercise. No alteration in the abundance and phosphorylation of proximal members of the insulin-signalling cascade in skeletal muscle, including the insulin receptor and IRS-1 were found. A major finding however, was the significant increase in the serine phosphorylation of a known downstream signalling protein, Akt (1.5 fold, p ≤0.05) following an acute bout of exercise and exercise training. This was matched by the observed increase in protein abundance of SHPTP2 (1.6 fold, p ≤0.05) a protein tyrosine phosphatase, in the cytosolic fraction of skeletal muscle following endurance exercise. These data suggest a small positive role for SHPTP2 on insulin stimulated glucose transport consistent with transgenic mice models. Further studies were aimed at examining the gene expression following a single bout of either resistance or endurance exercise. There were significant transient increases in IRS-2 mRNA concentration in the few hours following a single bout of both endurance and resistance exercise. IRS-2 protein abundance was also observed to significantly increase 24-hours following a single bout of endurance exercise indicating transcriptional regulation of IRS-2 following muscular contraction. One final component of this PhD project was to examine a second novel insulin-signalling pathway via c-Cbl tyrosine phosphorylation that has recently been shown to be essential for insulin stimulated glucose uptake in adipocytes. No evidence was found for the tyrosine phosphorylation of c-Cbl in the skeletal muscle of Zucker rats despite demonstrating significant phosphorylation of the insulin receptor and Akt by insulin treatment and successfully immunoprecipitating c-Cbl protein. Surprisingly, there was a small but significant increase in c-Cbl protein expression following insulin-stimulation, however c-Cbl tyrosine phosphorylation does not appear to be associated with insulin or exercise-mediated glucose transport in skeletal muscle.

Effects of strength, flexibility and moderate intensity cardiovascular exercise on measures of fitness in sedentary women

The maintenance of functional physical fitness across the lifespan depends upon the presence or absence of disease, injury, and the level of habitual physical activity. The prevalence of sedentariness rises with increasing age culminating in 31% of elderly women being classified as leading a sedentary lifestyle. Exercise prescription that involves easily accomplished physical activity may result in the maintenance of mobility into old age through a reduction in the risk of premature death and disablement from cardiovascular disease and a reduction in the risk of falls and injuries from falls. It may be that short bouts of physical activity are more appealing to the sedentary and to those in full time employment than longer bouts, and it may be that short bouts of exercise, performed three times per day, can improve physical fitness. The purpose of this study was therefore to examine the problem: Does exercise session duration, initial cardiovascular fitness, and age group effect changes in functional physical fitness in sedentary women training for strength, flexibility and aerobic fitness? Twenty-three, sedentary women aged between 19 and 54 years who were employed at a major metropolitan hospital undertook six weeks of moderate intensity physical activity in one of two training groups. Participants were randomly allocated to either short duration (3 x 10 minute), or long duration (30 minute), exercise groups. The 3 x 10 minute group (n=13), participated in three, 10 minute sessions per day separated by at least 2 hours, 3 days per week. The 30 minute group (n=10), participated in three 30 minute sessions per week. The total amount of work was similar, with an average of 129 and 148 kcal training day for the 3 x 10 minute and 30 minute groups, respectively. The training program incorporated three walking and stair climbing courses for aerobic conditioning, a series of eleven static stretches for joint flexibility, and isotonic and isometric strength exercises for lower and upper body muscular strength. Measures of functional strength, functional flexibility and cardiovascular fitness were assessed prior to training, and immediately following the six week exercise program. A two way analysis of variance (Group x Time) was used to examine the effect of training and group on the dependent variables. The level of significance, 0.05 was adopted for all statistical tests. Mean hand grip strength showed for both groups no significant change over time for the 3 x 10 minute group (30.7kg to 31.7kg) and 30 minute group (30.2kg to 32.4kg). Leg strength showed a trend for improvement (p=0.098) in both the 3 x 10 minute and 30 minute training groups representing a 15% and 18% improvement, respectively. Combined right and left neck rotation significantly improved in the 3 x 10 minute group (82.8° to 92.0°) and 30 minute group (82.5° to 91.5°). Wrist flexion and extension improved significantly in 3 out of the 4 measurements. Left wrist flexion improved significantly by an average of 7.0% for the 3 x 10 minute and 4.9% for the 30 minute group. Right and left wrist extension improved significantly in the 3 x 10 minute and 30 minute training groups (5.9% and 6.8%, respectively). Hip and spine flexibility improved 3.4cm (35.2cm to 38.6cm) in the 3 x 10 minute group, and 6.6cm (37.4cm to 44.0cm) in the 30 minute group. There was a significant improvement in cardiovascular fitness for both groups representing a 22% improvement in the 3 x 10 minute group (27.2 to 33.2 ml kg min), and a 25% improvement in the 30 minute group (27.5 to 34.4 ml -kg min). No significant difference was shown in the degree of improvement in cardiovascular fitness over six weeks of training for subjects of either low or moderate initial aerobic fitness. Grip strength showed no significant changes over time for either the young-aged (19-35 years) or middle-aged (36-54 years) groups. Leg strength showed a trend for improvement (p=0.093) in the young-aged group (63.5kg to 71.9kg) and middle-aged group (69.3kg to 85.8kg). Neck rotation flexibility improved a similar amount in both the young and middle aged groups representing an improvement of 9.9° and 8.0° respectively. There was significant improvement in two of the four measures of wrist flexibility. Hip and spine flexibility was significantly greater in the young-aged group compared to the middle-aged group (38.5cm and 30.7cm, respectively). There was a significant improvement in hip and spine flexibility over the six week training program representing an increase in reach of 6.5cm for the young age group and 4.9cm for the older group. The middle-aged subjects had significantly lower cardiovascular fitness than their younger peers, scoring 22.8 and 30.7 ml -kg min, respectively. Cardiovascular fitness improved a similar amount in both age groups representing a significant improvement of 23.8% and 28.1% for the younger-aged and middle-aged subjects, respectively. The findings of this study suggest that short bouts of exercise may be equally as effective as longer bouts of exercise for improving the flexibility and cardiovascular components of functional physical fitness in sedentary young and middle aged women. Additionally short bouts of exercise may be more attractive than longer bouts of exercise for the beginning exerciser as they may more easily fit into the busy lifestyle encountered by many people in today's society. Sedentary young and middle-aged women should benefit from static flexibility exercises designed to improve and/or maintain functional flexibility and thus maintain mobility and reduce the incidence of muscular injury. Regular, brisk walking, incorporating some stair climbing, is likely to be beneficial in improving cardiovascular health and perhaps also in improving leg strength, thereby helping to improve and maintain functional physical fitness for both young and middle-aged sedentary women.

Information-based regulation of high-velocity foot-targeting tasks

Judging time-to-contact with a target is an important criterion for avoiding harm in everyday walking and running tasks, and maximizing performance in high-velocity sporting tasks. The information-based regulation of step length and duration during target-directed locomotion was examined in relation to gait mode, approach velocity, target task, expertise, and sporting performance during a series of four experiments. The first three experiments examined novice performers (Each n=12, 6 males, 6 females), whilst the last experiment examined expert gymnasts (n=5). Two reference strips with alternating 50cm black and white intervals were placed on either side of the approach strip for all of the experiments. One 50Hz-panning video camera filmed the approach from an elevated position. In Experiment 4, two stationary 250Hz cameras filmed the post-flight performance of the gymnastic vaults and, in addition, two qualified judges provided a performance score for each vaulting trial. The panning video footage in each experiment was digitized to deduce the gait characteristics. In Experiment 4, the high-speed video footage was analyzed three-dimensionally to obtain the performance measures such as post-flight height. The utilization of visual stimulus in target-directed locomotion is affected by the observer's state of motion as characterized by the mode of locomotion and also often the speed of locomotion. In addition, experience plays an important role in the capacity of the observer to utilize visual stimulus to control the muscular action of locomotion when either maintaining or adjusting the step mechanics. The characteristics of the terrain and the target also affect the observer's movement. Visual regulation of step length decreases at higher approach speeds in novice performers, where as expert performers are capable of increasing visual regulation at higher approach speeds. Conservatism in final foot placement by female participants accounts for the observed increase in distance from the critical boundary of the obstacle relative to toe placement. Behavioural effects of gender thus affect the control of final foot placement in obstacle-directed locomotion. The visual control of braking in target-directed locomotion is described by a tau-dot of-0.54. When tau-dot is below -0.54 a hard collision with the obstacle will occur, however, when tau-dot is above -0.54, a soft collision with the target will occur. It is suggested that the tau-dot margin defining the control of braking reveals the braking capacity of the system. In the target-directed locomotion examined a tau-dot greater than -0.70 would possibly exceed the braking capacity of the system, thus, leading to injury if performed. The approach towards the take-off board and vaulting horse in gymnastics is an example of target-directed locomotion in sport. Increased visual regulation of the timing and length of each step is a requirement for a fast running approach, a fundamental building block for the execution of complex vaults in gymnastics. The successful performance of complex vaults in gymnastics leads towards a higher judge's score. Future research suggestions include an investigation of visual regulation of step length in curved target-directed locomotion.