Peripheral insulin resistance is characterised by reduced insulin-stimulated glucose uptake in skeletal muscle and adipose tissue, and the condition represents one of the earliest hallmarks in the development of type 2 diabetes (T2D). In patients with T2D, protein expression of the insulin-stimulated glucose transporter, GLUT4, is reduced in adipose tissue, but preserved in skeletal muscle. Transgenic studies in rodents provide evidence that overexpression of GLUT4 selectively in either skeletal muscle or adipose tissue enhances whole-body insulin action. Since skeletal muscle accounts for the majority of insulin-stimulated glucose disposal, the effect of adipose tissue GLUT4 on insulin sensitivity is thought to be secondary to an altered secretion of adipokines which affect insulin action in muscle, in the context of a ‘metabolic crosstalk’ between insulin sensitive tissues. Increasing GLUT4 expression in skeletal muscle and adipose tissue could be an effective therapy in the treatment of insulin resistance and T2D. Exercise training increases GLUT4 protein expression in skeletal muscle of patients with T2D. This adaptation occurs in the face of enhanced insulin sensitivity, and results from the cumulative and transient increase in GLUT4 mRNA following each acute exercise bout. Less is known regarding the regulation of skeletal muscle GLUT4 expression by a single bout of exercise in patients with T2D, or the effect of exercise training on GLUT4 expression in adipose tissue. / The primary aim of the studies undertaken for this thesis was to enhance understanding of exercise-mediated GLUT4 expression in skeletal muscle and adipose tissue of patients with T2D. The first investigation determined the effect of a single bout of exercise on skeletal muscle GLUT4 mRNA, and the signalling pathways which regulate GLUT4 expression, in patients with T2D and healthy control volunteers, matched for age and BMI. Increased (p<0.05) expression of GLUT4 and PGC-1α mRNA, together with increased (p<0.05) phosphorylation of AMPK and p38 MAPK was observed following exercise in patients with T2D, to a similar extent as in age- and BMI-matched control subjects. These findings lead to the conclusion that exercise-mediated regulation of GLUT4 expression is normal in patients with T2D. The second investigation of this thesis sought to identify the effect of a 4 week exercise training program on skeletal muscle and adipose tissue GLUT4 expression in patients with T2D. It was found that exercise training increased (p<0.05) GLUT4 protein expression by ~36% and ~20% in adipose tissue and skeletal muscle, respectively. These adaptations occurred in the absence of changes in insulin sensitivity or plasma levels of adipokines, adiponectin and resistin. Accordingly, the third study of this thesis sought to identify novel adipokines that regulate peripheral glucose metabolism in an adipocyte model of GLUT4 overexpression. Amyloid precursor protein (APP) was reduced (p<0.05) in culture media of GLUT4 overexpressing adipocytes, and the APP cleavage product, amyloid-beta (Aβ), reduced (p<0.05) insulin-stimulated Akt phosphorylation in L6 myocytes in vitro. / These observations lead to the conclusion that increased adipose tissue GLUT4 expression may influence whole body glucose metabolism through reduced levels of Aβ. The primary aim of the final study undertaken was to identify novel changes in the abundance of proteins in skeletal muscle following exercise training in patients with T2D, including proteins of glucose metabolism, which may regulate of GLUT4 expression. Exercise training altered the abundance of several proteins involved in energy metabolism, as well as some novel proteins which may play a role in cytoskeleton interactions with mitochondria. In summary, this thesis demonstrated that skeletal muscle from patients with T2D responds normally to an acute exercise bout in terms of increased GLUT4 mRNA expression. In addition, it was shown that exercise training increased GLUT4 protein expression, not only in skeletal muscle, but also in adipose tissue of patients with T2D. This is significant because adipose tissue GLUT4 overexpression enhances insulin sensitivity. Data from this thesis suggest that improvements in insulin sensitivity may be secondary to altered secretion of Aβ from adipose tissue. Collectively, the findings provide a number of therapeutic targets for the treatment of insulin resistance and T2D.

No description available.

Androstenedione, 4-androstenediol, 5-androstenediol, 19-norandrostenediol and 19-norandrostenedione are commonly referred to as "Andro" prohormones. Over the last few years, supplementation using these prohormones has been aggressively marketed to the general public. Supplement manufacturers often claim that Andro use improves serum testosterone concentrations, increases muscular strength and muscle mass, helps to reduce body fatness, enhances mood, and improves sexual performance. However, to date, most studies contradict these claims. In contrast, several studies using oral Andro related prohormones show that Andro use can abnormally elevate estrogen related hormones as well as alterations in hormonal markers (i.e., abnormal elevations in serum estrogen) thought to increase a person's risk for developing prostate or pancreatic cancers. In addition, most studies also indicate that significant declines in high-density lipoproteins occur leading to an increased cardiovascular disease risk. Thus, to date, the current research base suggests that Andro prohormone use does not support manufacturer claims. But it does suggest there should be strong concerns regarding long-term oral Andro prohormone use, especially regarding its effects on blood lipids and estrogen hormone profiles.

Resistance training (RT)-induced skeletal muscle hypertrophy is partly responsible for the RT-induced increase in strength. Previously, we reported that exercise repetition load played a minimal role in the promotion of RT-induced gains in hypertrophy and strength gains in RT-naïve participants performing RE to volitional failure. Thus, the main aim of this study were to determine the effects of 12 weeks of RT on muscle strength and hypertrophy in a trained population. 49 resistance-trained men (mean ± SEM, 23 ± 1 years, 85.9 ± 2.2 kg, 181 ± 1 cm) were randomly allocated into a lower load-high-repetition group (HR, n=24) or a higher load-low-repetition group (LR, n=25). Repetition load was set so that volitional lifting failure was achieved within the repetition ranges of 20-25 (~35-50% of 1RM) for HR or 8-12 for LR (~70-85% of 1RM). Strength as one repetition maximum (1RM) was assessed pre and post. Changes in lean body mass (LBM), appendicular lean mass (ALM) and leg lean mass (LLM) were assessed using dual-energy x-ray absorptiometry (DXA). There were significant increases in strength in all exercises with no differences between groups (p > 0.05) with the exception of bench press where LR showed a greater increase in 1RM than HR (p = 0.012). Similarly, LBM, ALM, and LLM increased significantly following training in the HR group (1.0 ± 0.9kg, p < .001; 0.8 ± 1.1 kg, p < 0.05; 0.7 ± 0.9 kg, p < 0.01 respectively) and the LR group (1.6 ± 1.4 kg, p < .001; 1.0 ± 1.2 kg, p < 0.05; 0.7 ± 1.0 kg, p < 0.01 respectively) with no significant differences between groups (all p > 0.05). These data show that RE performed to volitional failure using either HR or LR induces similar adaptations strength and lean mass accrual in young resistance-trained men. / Thesis / Master of Science in Kinesiology / Resistance training (RT) results in an increase in muscle growth and an increase in strength. Previously, we have shown in young untrained males, that when exercise is performed until failure, or until the weight can no longer be lifted, that gains in muscle and strength were similar with the use of either light or heavy weights. The purpose of the study was to determine the effects of 12 weeks of RT on muscle growth and strength in young men who were already regularly participating in resistance exercise when performing either lower load high repetition RT (HR) or higher load low repetition RT (LR). Maximum strength and changes in muscle mass were assessed prior to and upon completion of the training protocol. Following 12 weeks of RT both groups increased muscle mass and strength to a similar extent with the exception of bench press which increased more in the LR group.

No description available.

Purpose: In response to resistance exercise training, it has been shown that individuals with a previous training history acquire muscle volume at an accelerated rate. This phenomenon may be attributed, in part, to the myonuclear enrichment resulting from the proliferation of muscle progenitor cells, which promotes essential protein synthesis following subsequent muscle training. As a highly energy demand tissue, the successful hypertrophy of muscle fiber depends on mitochondrial biogenic progression. Moreover, the majority of genes that encode mitochondrial proteins are within nuclear genome. Therefore, in this study, we investigated the effect of increased number of myonuclei in response to the previous resistance exercise preconditioning on mitochondrial adaptations to subsequent resistance training. Our central hypothesis was that pre-trained muscles would show an accelerated acquisition of training-induced mitochondrial function leading to a greater skeletal muscle hypertrophy compared to previously non-trained muscles and this may be associated with increased number of myonuclei in the pre trained muscles. Methods: Thirty-two Sprague-Dawley rats were randomly assigned to four groups (n=8 per group) which include control, pre-training, training, and retraining group. Resistance exercise training was carried out by ladder climbing with weights attached to the tail at ages of either 8- (pre-training) and 36-week-old (training), or both (retraining). Each training session consisted of 3 sets of 5 repetitions, and the training protocol was performed every third day for 8 weeks. At 44 weeks of age, specific muscle groups were carefully collected and stored at -80 °C until further analyses. 4', 6-Diamidino-2-phenylindole staining, hematoxylin & eosin staining, cytochrome c oxidase and succinate dehydrogenase staining were performed. Western blotting and immunohistochemstry were performed to assess the abundance of mitochondrial regulatory proteins and the mitochondrial content. In complementary in vitro studies, confluent L6 myoblast cells were further grown in differentiation media for 4 days with or without insulin-like growth factor 1 (50 ng/ml) supplementation. Mitochondrial gene expression levels and mitochondrial respiratory function were assessed after 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR, 1 mM), a 5' AMP-activated protein kinase activator, treatment. Results: Myonuclei numbers were higher in training and retraining groups than control group (all, p &lt; 0.05), suggesting that ladder climbing training protocol increased myonuclei number. There was a significantly higher level of myonuclei number in pretraining group compared to the control group indicating that the acquired myonuclei during exercise preconditioning were retained over the 20-week detraining period. Muscle cross-sectional area, mitochondrial content and mitochondrial enzymatic activities (COX and SDH) were significantly greater in retraining group compared to training group (p &lt; 0.01, p &lt; 0.01 and p &lt; 0.05, respectively). In in vitro study, L6 myotubes preconditioned with IGF-1 showed increased myonuclei numbers within each myotube and presented a higher level of mitochondrial gene expression and oxygen consumption rate under AICAR treatment condition. Conclusions: These data provide physiological evidence that pre-trained muscle with more myonuclei make the muscles more responsive to subsequent training in terms of muscle hypertrophy and mitochondrial remodeling. Furthermore, this study provides a proof-of-concept of biological processes underlying potential nuclear-mitochondrial interplay during muscle hypertrophy. These findings warrant future studies to identify a novel target for mitochondrial medicine to treat muscle atrophy. / Kinesiology

The purpose of this thesis was to investigate the effects of nutritional supplementation following resistance exercise on protein metabolism, muscle glycogen resynthesis rate, hormonal responses and training status through two unique investigations. The purpose of the first investigation was to determine the effect of post-resistance exercise glucose supplementation upon skeletal muscle fractional synthetic rate (FSR), urinary urea excretion, and whole body and myofibrillar protein degradation (WBPD and MPD, respectively). Eight healthy young males performed unilateral knee extensor resistance exercise(8sets/~1 0reps/~85% 1 RM) such that the non-exercised limb served as a control. They received a carbohydrate (CHO) supplement (1g/kg) or placebo (PL) immediately (t=Oh) and 1 h (t=+1 h) following exercise. FSR was determined for both exercised (EX) and control (CON) limbs by incremental L-[1-13C]leucine enrichment of biopsy samples of vastus lateralis over -10 hours post-exercise. Plasma insulin and glucose were determined at t= -1.5, 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, -10, and -10.5h post-exercise. MPD and WBPD were estimated from 24 hr urinary 3-methylhistidine (3-MH) and L-[1-13C]leucine flux, respectively, and whole body net protein balance was estimated from 24 hr urinary urea excretion. Plasma insulin concentration was greater (p<0.01) at 0.5, 0.75, 1.25, 1.5, 1.75 and 2 h in the CHO compared to PL condition, as was plasma glucose at 0.5 and 0. 75 h (p<0.05). FSR was 36.1% greater in the CHO/EX leg than in the CHO/CON leg (p=N.S.) and 6.3% greater in the PUEX leg than in the PUCON leg(p=N.S.). 3-MH excretion was lower in the CHO (110.43 ± 3.62 J μmol/g creatinine) than PL condition (120.14 ± 5.82)(p<0.05) as was urinary urea nitrogen(8.60 ± 0.66 g/g creat vs. 12.28 ± 1.84)(p<0.05). These findings suggest that CHO supplementation (1g/kg) immediately and 1h following resistance exercise can significantly decrease myofibrillar protein breakdown and urinary urea excretion, thus resulting in a more positive muscle and whole body protein balance. The purpose of the second investigation was to determine the effect of various nutritional supplements upon whole body protein synthesis, urinary urea excretion, and whole body and myofibrillar protein degradation (WBPD and MPD respectively). Ten healthy young male resistance athletes performed a whole body circuit set workout (9 exercises/3 sets/80% 1 Repitition Maximum). Exercises for the legs were performed unilaterally so that the non-exercised leg served as a control They received a carbohydrate (CHO) supplement (1g/kg), a mixed CHO/PRO/FAT supplement (isoenergetic to CHO supplement)(68% CHO, 22% PRO, 10% FAT) or placebo (PL) immediately (t=Oh) and 1 h (t=+1h) following exercise. Immediately following exercise muscle glycogen was significantly lower (p<0.05) in vastus lateralis of the exercised leg than in the control leg immediately post-exercise in all three conditions. Both the CHO and CHO/PRO/FAT supplements resulted in significantly greater increases (p<0.05) in plasma insulin and glucose post-exercise than PL. The CHO and CHO/PRO/FAT also resulted in significantly greater(p<0.05) rates of muscle glycogen resynthesis vs. Placebo. No significant differences were observed between the three conditions for plasma testosterone and cortisol concentration post-exercise. Similarly, no differences were observed between the three conditions for urinary creatinine, and 3-MH and urea nitrogen excretion. Thus, nutritional supplements do not appear to decrease myofibrillar protein degradation as indicated by 3-MH and urea nitrogen excretion in highly trained resistance athletes. Taken together, the two studies suggest that highly trained resistance athletes and untrained individuals both benefit from nutritional supplementation following resistance exercise, but may do so through different mechanisms. / Thesis / Master of Science (MS)

Ten subjects were randomly assigned to train one arm with ballistic movements (BT), whereas the other arm trained with ballistic and heavy resistance movements (BT+HRT). The training program consisted of three training sessions per week, over a ten week period. The BT arm executed ten sets of six maximal ballistic elbow extension actions (10% MVC), whereas the BT+HRT arm executed five sets of six repetitions of maximal ballistic actions followed by five sets of five to eight repetitions of heavy resistance elbow extension actions. After training, evoked twitch contractile properties, ballistic, 1 RM, and isometric MVC measures were analyzed. Incorporated with all performance measures were EMG recordings of the agonist (AG) triceps and antagonist (ANT) biceps. Muscle biopsies of triceps were also taken to determine muscle fibre type composition, and fibre area. The BT+HRT arm demonstrated a significant decrease in the percent population of type IIb fibres (22% to 18. 8%). Furthermore, the BT+HRT arm produced hypertrophy, type IIa (6184 to 7086 μm²) and IIb (5714 to 6734 μm²) fibre areas increased, whereas type I fibre areas (3503 to 3828 μm²) did not significantly increase, after training. In contrast, the BT arm and control arm did not display fibre transformation or hypertrophy after training. Triceps evoked twitch peak torque increased for only the BT+HRT arm (12.5 to 13.8 N·m). Furthermore, the 1 RM increased significantly in the BT+HRT arm (~24%) but did not change significantly in the BT arm. However, ballistic and isometric MVC PT values increased similarly in both the BT (19.6 to 23.5 N·m; 45.4 to 52.6 N·m) and the BT+HRT (19.6 to 23.6 N·m; 49.6 to 56.0 N·m) arms. The EMG results corresponded to the performance results in that triceps AEMG in the 1 RM test tended to increased more after HRT (0.71 to 1.01 mV) than only BT (0.72 to 0.81 mV), but in the ballistic (HRT= 0.63 to 0.79 mV; BT= 0. 62 to 0. 73 mV) and isometric MVC performance measures (HRT= 0.80 to 0.84 mV; BT= 0.80 to 0.87 mV), the AEMG results were similar. Supplementary HRT caused muscle hypertrophy, particularly of the type II fibres, but did not promote improvement in ballistic performance with loads equal to or less than 10% of maximal isometric force. / Thesis / Master of Science (MS)

Resistance exercise training (RET) can lead to muscle hypertrophy; however, the relative contribution that exogenous (protein supplementation and specific training variables) versus endogenous (biology inherent to the individual) factors have on RET-induced muscle hypertrophy is controversial. In Study 1, we provided an evidence-based conclusion that protein supplementation during periods of RET results in a small but statistically significant increase in RET-induced muscle hypertrophy. In Study 2, we corroborate previous research and observed that the amount of mass lifted per repetition (load) did not determine RET-induced muscle hypertrophy in resistance-trained men when RET was performed to volitional fatigue. In Study 4, we observed similar muscle fibre activation following resistance exercise with lighter versus heavier loads when both were lifted until volitional fatigue. In Studies 2 and 3, we observed no relationship between circulating anabolic hormones (e.g., testosterone) and RET-induced muscle hypertrophy. Nonetheless, in Study 3, we found significantly greater muscle androgen receptor content in the top versus the bottom quintile of respondents for muscle hypertrophy following 12 weeks of RET indicating that androgen receptor content, and not circulating androgen concentration, may be an important determinant of hypertrophy. Finally, in Study 5, we observed that RET-induced muscle hypertrophy was an consistent within an individual (independent of load and limb) but considerably different between participants. Together, these data suggest that the exogenous factors we studied – protein supplementation and load (when RET was performed to volitional fatigue) – had a relatively small influence on RET-induced muscle hypertrophy. In contrast, we found that endogenous variables, such as intramuscular androgen receptor content and likely other genetic influences, appear to contribute more to the significant heterogeneity seen in RET-induced muscle hypertrophy. Future research in this area should prioritize understanding the biology that underpins the individual variability in RET-induced muscle hypertrophy. / Thesis / Doctor of Philosophy (PhD) / Resistance exercise training (RET) increases muscle size (hypertrophy); however, the relative influence that protein supplementation, specific training variables, and individual (genetic) variation have on the RET-induced hypertrophy is controversial and largely unknown. Broadly, data in this thesis show that protein supplementation slightly augments RET-induced hypertrophy, and that the magnitude of RET-induced hypertrophy may be related to the number of androgen (e.g., testosterone) receptors inside an individual’s muscle. In contrast, we found that neither load nor hormones affect RET-induced hypertrophy. Interestingly, data in this thesis also show that RET-induced hypertrophy is consistent within an individual but varies considerably between people, which illustrates the greater influence that individual variation has on RET-induced hypertrophy. We conclude that when RET is performed with a high degree of effort, protein supplementation and specific training variables confer a relatively small benefit on RET-induced hypertrophy compared to the influence of biological variability between people.

INTRODUCTION Rheumatoid arthritis (RA) is a disease of chronic inflammation in the joints and organs. RA patients exhibit 4-fold increased incidence of CVD, increased prevalence of insulin resistance (IR) and increased mortality. Aerobic and resistance training (RT) programs have been suggested for the management of RA symptoms and reduction of comorbidities, including insulin resistance. Exercise has been shown by recent evidence to be safe and beneficial in RA patients. RT has been documented to improve inflammation and insulin sensitivity. The present study was undertaken to examine the impact of a sixteen week intensive training regimen on disease status, body composition, markers of inflammation and indicators of insulin resistance in RA patients undergoing infliximab therapy, a potent RA treatment.METHODS30 RA patients were randomized into exercise (EX) or control (C) groups. EX patients underwent a 16-week supervised, intensive, progressive and individualized resistance training regimen. Participants were monitored by professional fitness trainers during all exercise sessions. Subjects were assessed prior to and after intervention. Assessments included disease status, strength and functional testing, anthropometrical and body composition analysis, analysis of markers of inflammation and assessment of insulin sensitivity.RESULTS EX subjects significantly increased in strength and functional ability without worsening of disease state, and increased lean mass from baseline. Fat mass was significantly reduced in EX. Glucose and resistin levels increased significantly following EX intervention. Mean IR was unchanged, but EX subjects with elevated IR did show improvement following training. Regression analysis indicates duration of infliximab therapy to be correlated with improved insulin sensitivity.CONCLUSIONS RA patients taking infliximab tolerated an intensive resistance training program. Participants increased strength and lean mass while decreasing fat mass and displayed improved functional capacity. Disease status was not worsened by the regimen. Though the mean measure of IR did not improve, those patients with the most adverse scores did show improvement following the intervention. Furthermore, regression analysis indicates that infliximab treatment duration was linked to reduced IR. In conclusion, resistance training improved strength and functional ability in RA patients taking infliximab without disease degradation, and may help reduce IR in those patients with elevated resistance.