Endurance Exercise Intervention Research Articles

Endurance exercise improves function in individuals with Parkinson's disease: A meta-analysis.

Current evidence has shown that exercise can reduce symptoms of Parkinson's disease (PD). However, previous studies indicated mixed results, possibly because of variability in terms of the nature of the exercise interventions. The purpose of this study was to perform a metaanalysis of current evidence from endurance exercise intervention studies for effects on the United Parkinson's Disease Rating Scale (UPDRS) in individuals with PD. A systematic literature search in six electronic databases was performed and two independent reviewers screened the title and abstract of 1106 records captured by the initial search. Inclusion criteria for full-text review were (A) peer-reviewed English-language publications, (B) randomized controlled trials that compared an endurance exercise intervention group to a non-exercising control group, and (C) an outcome measure which included the UPDRS total score or section III (motor) subscore. From the title/abstract screening, the same independent reviewers assessed 245 full-text articles for eligibility. Of the fulltext articles reviewed 7 articles were included in our meta-analysis, 238 were excluded for the following reasons: 147 did not meet endurance exercise criteria, 53 were review/systematic reviews, 34 were conference abstracts or posters, 2 were editorial or commentary, 1 was a study protocol, and 1 was unpublished. The d index was used to calculate the difference between means of different groups within individual studies, and a weighting factor or w was used to calculate the effect size across studies. Overall, d index was found to be -0.32 with 95% confidence interval, CI (-0.09, -0.56) found to be statistically significant indicating a positive effect of endurance exercise in UPDRS scores. In conclusion, this meta-analysis supports integrating endurance exercise training, as defined by ACSM, into treatment of PD.

“It Takes Two To Tango”, Exercise Modifies Skeletal Muscle Mitochondria And Lipid Droplets Closeness

PURPOSE: Intramyocellular lipids (IMCL), stored in lipid droplets (LD), are known to be a hallmark of skeletal muscle insulin resistance. Chronic exercise (training) increases IMCL while also increasing insulin sensitivity (IS), a paradigm known as the athlete’s paradox. Mitochondria (M), the powerhouse of the cells, are responsible to transform LD content into energy. The closeness of these 2 organelles in the different subcellular compartments (intramyofribrillar (IMF) and subsarcolemmal (SSL)) and how they change with training are not yet known. The purpose of this study was to examine exercise induced changes in LD and M closeness in insulin resistant non-diabetic subjects. METHODS: In a nested case-control study, 12 cases (6F/6M) underwent a 4-months supervised endurance exercise intervention. 12 insulin sensitive subjects matched by age and gender served as controls (C). LD, M and the surface in contact with each other, were assessed in muscle biopsies with electron microscopy. IS was measured by hyperinsulinemic euglycemic clamp. VO2peak was measured by GXT and body composition by DEXA. RESULTS: Although training improved IS by 45±8% (P<0.05), increased VO2peak by 13.2±4.4% (P<0.05), reduced body fat by 3.9±1.2% (P<0.05), cases remained significantly different from C. M increased in IMF and SSL (54.7±15.1% and 78.2±20.5% respectively, P<0.05). LD increased in IMF (51.8±18.1%) and decreased in (SSL 20.7±8.3%, both P<0.05). Contact between M and LD increased significantly only in IMF (65.1±26.3%, P<0.05). While SSL LD were negatively correlated with IS at baseline, changes in overall LD with intervention were related with improvements in IS. SSL LD correlated with body adiposity, but not IMF LD. CONCLUSIONS: With endurance training, the closeness of M and LD increased only in the contractile region, i.e. the IMF compartment. At the same time, the amount of M and LD increased in this compartment. This observation confirms what is observed in healthy and athletic individuals, which suggests that IMCL are used for fuel. At the contrary, LD decreased in the SSL region while M increased in this compartment. Our observations are of interest, as IMCL are known to be involved in the mechanisms leading to insulin resistance in sedentary muscle, possibly explaining the observation in the SSL region.

Effectiveness of endurance exercise training in patients with coronary artery disease: A meta-analysis of randomised controlled trials

Exercise interventions apparently reduce the risks of and prevent coronary artery disease (CAD). Developing an exercise intervention for patients with CAD is a rapidly expanding focus worldwide. The results of previous studies are inconsistent and difficult to interpret across various types of exercise programme. This study aimed to update prior systemic reviews and meta-analyses in order to determine the overall effects of endurance exercise training on patients with CAD. The databases (PubMed, Medline, CINAHL, EMBASE and Cochrane Library) were searched for the interventions published between January 1, 2000, and May 31, 2015. Comprehensive meta-analysis software was used to evaluate the heterogeneity of the selected studies and to calculate mean differences (MDs) while considering effect size. A total of 18 studies with 1286 participants were included. Endurance exercise interventions at a moderate to high training intensity significantly reduced resting systolic blood pressure (MD: -3.8 mmHg, p = 0.01) and low-density lipoprotein cholesterol (MD: -5.5 mg/dL, p = 0.02), and increased high-density lipoprotein cholesterol (MD: 3.8 mg/dL, p < 0.001). There were also significant positive changes in peak oxygen consumption (MD: 3.47 mL/kg/min, p < 0.001) and left ventricular ejection fraction (MD: 2.6%, p = 0.03) after the interventions. Subgroup analysis results revealed that exercise interventions of 60-90 minutes per week with a programme duration of >12 weeks had beneficial effects on functional capacity, cardiac function and a number of cardiovascular risk factors. Endurance exercise training has a positive effect on major modifiable cardiovascular risk factors and functional capacity. Nurses can develop endurance exercise recommendations for incorporation into care plans of clinically stable CAD patients following an acute cardiac event or revascularisation procedure.

Effects Of Endurance Training On Muscular V’O2 Kinetics In Type 2 Diabetes Patients

PURPOSE: Maximal V’O2 is known to increase with endurance exercise interventions. Recently, a method has been developed to assess muscular V’O2 (V’O2musc) kinetics from heart rate (HR) and pulmonary V’O2 responses to work rate changes, which allows a better differentiation between cardiovascular system and muscular metabolism. Cardiorespiratory kinetics were analyzed in type 2 diabeties subjects before and after an endurance exercise intervention. METHODS: 9 male subjects (61 ± 9 years, 33 ± 5 kg·m−2) were tested for peak V’O2 (V’O2peak), glycemic parameters and cardiorespiratory kinetics using pseudo randomized binary work rate changes (30/80 W). To estimate V’O2musc and cardiorespiratory kinetics, the method of Hoffmann et al. (2013) was applied. Kinetics were summarized by maximum of cross correlation functions (CCFmax) and equivalents of time constants. Two pre-tests (Pre I, Pre II) within a 4 week period and a post-test after 12 weeks of endurance training were performed. Differences between the tests were analyzed via a two factorial ANOVA. P<= 0.05 was considered significant. RESULTS: Table 1 shows the results of Pre I, Pre II and Post tests (mean +− SD, * significantly different from Post). CONCLUSION: Endurance training improves both, V’O2musc and heart rate kinetics in type 2 diabetes patients. This was in accordance with the increase in V’O2peak. In contrast, no changes in glycemic parameters could be observed. V’O2musc kinetics, assessed via moderate WR changes and independent of motivation, can be seen as an indicator for cardiorespiratory fitness and might be useful to measure increases in cardiorespiratory regulation.Table: No title available.Reference: Hoffmann et al. (2013); EJAP, 113:1745-1754.

Mesenchymal stem cell therapy associated with endurance exercise training: Effects on the structural and functional remodeling of infarcted rat hearts

We tested the effects of early mesenchymal stem cell (MSC) therapy associated with endurance exercise on the structural and functional cardiac remodeling of rats with myocardial infarctation (MI). Male Wistar rats (40days old) were divided into 6 groups: control and exercise sham; control and exercise MI; and control and exercise MI MSC. MI was surgically induced and bone marrow-derived MSCs were immediately injected via caudal vein (concentration: 1×106 cells). Twenty-four hours later ET groups exercised on a treadmill (5days/week; 60min/day; 60% of maximal running velocity) for 12weeks. Structural and functional changes were determined by echocardiography. Contractility and intracellular global calcium ([Ca2+]i) transient were measured in myocytes from the left ventricular (LV) non-infarcted area. Calcium regulatory proteins were measured by Western blot. MI increased (p<0.05) heart, ventricular and LV weights and its ratios to body weight; LV internal dimension in diastole (LVID-D) and in systole (LVID-S) and LV free wall in diastole (LVFW-D), but reduced the thickness of interventricular septum in systole (IVS-S), ejection fraction (EF) and fractional shortening (FS). MI augmented (p<0.05) the times to peak and to half relaxation of cell shortening as well as the amplitude of the [Ca2+]i transient and the times to peak and to half decay. Early MSCs therapy restored LVFW-D, IVS-S and the amplitude and time to half decay of the [Ca2+]i transient. Early endurance exercise intervention increased (p<0.05) LVFW-S, IVS-S, EF and FS, and reduced the times to peak and to half relaxation of cell shortening, and the amplitude of the [Ca2+]i transient. Exercise training also increased the expression of left ventricular SERCA2a and PLBser16. Nevertheless, the combination of these therapies did not cause additive effects. In conclusion, combining early MSCs therapy and endurance exercise does not potentiate the benefits of such treatments to structural and functional cardiac remodeling in infarcted rats.

Fitness is a determinant of the metabolic response to endurance training in adolescents at risk of type 2 diabetes mellitus.

The purpose of this prospective cohort study was to determine whether changes in cardiorespiratory fitness are associated with the metabolic response to endurance training in adolescents at risk of type 2 diabetes mellitus (T2DM). Seventy-three overweight and obese adolescents completed a 6-month endurance exercise intervention. Total fat mass, trunk fat mass, visceral adipose tissue, and liver fat were assessed with dual energy X-ray absorptiometry and magnetic resonance imaging spectroscopy. The change in cardiorespiratory fitness with training was independently associated with reductions in BMI z-score (β = -0.09; P = 0.006), total fat mass (β = -1.40; P = 0.007), trunk fat mass (β = -0.70; P = 0.01), and liver fat (β = -1.80; P = 0.053). Adolescents within the highest tertile of change in fitness were 4.67 (95% CI: 1.15-13.73; P = 0.03), 11.90 (95% CI: 2.37-59.77; P = 0.002), and 6.21 (95% CI: 1.14-33.99; P = 0.035) times more likely to experience decreases in body weight, BMI, and liver fat compared with adolescents in the lowest tertile. The changes in adiposity and hepatic triglyceride content in response to endurance training are significantly related to the increase in cardiorespiratory fitness in adolescents at risk of T2DM.

Subsarcolemmal lipid droplet responses to a combined endurance and strength exercise intervention.

Muscle lipid stores and insulin sensitivity have a recognized association although the mechanism remains unclear. We investigated how a 12‐week supervised combined endurance and strength exercise intervention influenced muscle lipid stores in sedentary overweight dysglycemic subjects and normal weight control subjects (n = 18). Muscle lipid stores were measured by magnetic resonance spectroscopy (MRS), electron microscopy (EM) point counting, and direct EM lipid droplet measurements of subsarcolemmal (SS) and intramyofibrillar (IMF) regions, and indirectly, by deep sequencing and real‐time PCR of mRNA of lipid droplet‐associated proteins. Insulin sensitivity and VO2max increased significantly in both groups after 12 weeks of training. Muscle lipid stores were reduced according to MRS at baseline before and after the intervention, whereas EM point counting showed no change in LD stores post exercise, indicating a reduction in muscle adipocytes. Large‐scale EM quantification of LD parameters of the subsarcolemmal LD population demonstrated reductions in LD density and LD diameters. Lipid droplet volume in the subsarcolemmal LD population was reduced by ~80%, in both groups, while IMF LD volume was unchanged. Interestingly, the lipid droplet diameter (n = 10 958) distribution was skewed, with a lack of small diameter lipid droplets (smaller than ~200 nm), both in the SS and IMF regions. Our results show that the SS LD lipid store was sensitive to training, whereas the dominant IMF LD lipid store was not. Thus, net muscle lipid stores can be an insufficient measure for the effects of training.

A Methionine-Restricted Diet and Endurance Exercise Decrease Bone Mass and Extrinsic Strength but Increase Intrinsic Strength in Growing Male Rats1–3

Dietary methionine restriction (MR) has been suggested to be comparable to endurance exercise with respect to its beneficial effects on health. To further investigate the effects of MR and endurance exercise on growing bone, 7-wk-old male Sprague-Dawley rats were fed different L-methionine (Met)-containing diets with or without endurance exercise intervention (Ex; 0.86% Met, 0.52% Met, 0.17% Met, 0.86% Met-Ex, 0.52% Met-Ex, and 0.17% Met-Ex groups). After an 8-wk intervention period, exercise-trained rats had a 9.2% lower body weight (BW) than did sedentary rats (P < 0.05). Additionally, 0.17% Met–fed rats had 32% lower BW when compared with rats fed the other 2 diets (P < 0.05). Serum osteocalcin was lower in the 0.17% Met-Ex group compared with the other 2 exercise groups and the 0.17% Met group (P < 0.05). Serum concentrations of C-terminal telopeptide of type 1 collagen were lower in exercise-trained and 0.17% Met–fed rats than in sedentary rats and rats fed the other 2 diets (P < 0.05 for both). Rats fed the 0.17% Met diet had lower trabecular bone volume, bone mineralization activities, and bone mineral content (BMC; e.g., total, cortical, and spongy BMC) and bone mineral density (BMD; e.g., total and spongy BMD) indices compared with rats fed the other 2 diets (P < 0.05). Exercise-trained rats also had lower bone mineralization activity, trabecular osteoclast density, total BMC, cortical BMC, and total BMD compared with sedentary rats (P < 0.05). In total BMD, only the 0.17% Met-Ex group had values lower than the other 2 exercise groups and the 0.17% Met group (P < 0.05). Compared with rats fed the other 2 diets and sedentary rats, the femora of 0.17% Met–fed and exercise-trained rats, respectively, had smaller size and/or lower extrinsic strength but enhanced intrinsic biomechanical properties (P < 0.05). The results indicate that MR and endurance exercise caused lower whole bone mass, size, and/or strength but might enhance intrinsic bone strength. [Display omitted]

Identification of human exercise-induced myokines using secretome analysis

Endurance exercise is associated with significant improvements in cardio-metabolic risk parameters. A role for myokines has been hypothesized, yet limited information is available about myokines induced by acute endurance exercise in humans. Therefore, the aim of the study was to identify novel exercise-induced myokines in humans. To this end, we carried out a 1 h one-legged acute endurance exercise intervention in 12 male subjects and a 12 wk exercise training intervention in 18 male subjects. Muscle biopsies were taken before and after acute exercise or exercise training and were subjected to microarray-based analysis of secreted proteins (secretome). For acute exercise, secretome analysis resulted in a list of 86 putative myokines, which was reduced to 29 by applying a fold-change cut-off of 1.5. Based on that shortlist, a selection of putative myokines was measured in the plasma by ELISA or multiplex assay. From that selection, CX3CL1 (fractalkine) and CCL2 (MCP-1) increased at both mRNA and plasma levels. From the known myokines, only IL-6 and FGF 21 changed at the mRNA level, whereas none of the known myokines changed at the plasma level. Secretome analysis of exercise training intervention resulted in a list of 69 putative myokines. Comparing putative myokines altered by acute exercise and exercise training revealed a limited overlap of only 13 genes. In conclusion, this study identified CX3CL1 and CCL2 as myokines that were induced by acute exercise at the gene expression and plasma level and that may be involved in communication between skeletal muscle and other organs.

Endurance Exercise Alters Cellular Immune Status and Resistin Concentrations in Men Suffering from Non-insulin-dependent Type 2 Diabetes

It has been demonstrated that alterations of adipocytokines can alter immune status in type 2 diabetes. The present study investigated changes of adipocytokine plasma concentrations and cellular immune status in overweight men, suffering from non-insulin dependent type 2 diabetes (n=14, age 61.0±8.7 years, BMI 31.1±3.5 kg/cm2). Subjects underwent a 3 months endurance exercise intervention (twice per week for up to 45 min) cycling at a heart rate corresponding to a 2 mmol/l lactate threshold. Before and after the intervention testing for adipocytokines (leptin, adiponectin, resistin) and cellular immune status (including T memory-cells and regulative T-cells) was performed by RIA and FACS accordingly.The exercise intervention improved anthropometric and metabolic parameters of all subjects. We observed a significant decline for resistin and for the CD19+ B-cells. The CD4+CD25+CD127low Treg-cells decreased, however not statistically significant. All other parameters remained unchanged.In conclusion, even though only training twice a week, the exercise affected parts of the cellular immune system as well as resistin levels in men suffering from non-insulin dependent type 2 diabetes.

Resistance exercise, but not endurance exercise, induces IKKβ phosphorylation in human skeletal muscle of training-accustomed individuals

The mammalian target of rapamycin complex 1 (mTORC1) is considered an important role in the muscular adaptations to exercise. It has been proposed that exercise-induced signaling to mTORC1 do not require classic growth factor PI3K/Akt signaling. Activation of IKKβ and the mitogen-activated protein kinases (MAPKs) Erk1/2 and p38 has been suggested to link inflammation and cellular stress to activation of mTORC1 through the tuberous sclerosis 1 (TSC1)/tuberous sclerosis 2 (TSC2) complex. Consequently, activation of these proteins constitutes potential alternative mechanisms of mTORC1 activation following exercise. Previously, we demonstrated that mTOR is preferentially activated in response to resistance exercise compared to endurance exercise in trained individuals without concomitant activation of Akt. In the present study, we extended this investigation by examining IκB kinase complex (IKK), TSC1, MAPK, and upstream Akt activators, along with gene expression of selected cytokines, in skeletal muscles from these subjects. Biopsies were sampled prior to, immediately after, and in the recovery period following resistance exercise, endurance exercise, and control interventions. The major finding was that IKKβ phosphorylation increased exclusively after resistance exercise. No changes in TSC1, Erk1/2, insulin receptor, or insulin receptor substrate 1 phosphorylation were observed in any of the groups, while p38 phosphorylation was higher in the resistance exercise group compared to both other groups immediately after the intervention. Resistance and endurance exercise increased IL6, IL8, and TNFα gene expression immediately after exercise. The non-exercise control group demonstrated that cytokine gene expression is also sensitive to repeated biopsy sampling, whereas no effect of repeated biopsy sampling on protein expression and phosphorylation was observed. In conclusion, resistance exercise, but not endurance exercise, increases IKKβ phosphorylation in trained human subjects, which support the idea that IKKβ can influence the activation of mTORC1 in human skeletal muscle.

To resist or to endure: exercise mode matters in arterial structure and function

To resist or to endure: exercise mode matters in arterial structure and function

Effect of Acute Endurance and Resistance Exercise on Endocrine Hormones Directly Related to Lipolysis and Skeletal Muscle Protein Synthesis in Adult Individuals with Obesity

In subjects with obesity, the implementation of long-term exercise intervention increases lean tissue mass and lowers adipose tissue mass. However, data indicate a blunted lipolytic response, and/or skeletal muscle protein synthesis, when subjects with obesity are exposed to acute endurance or resistance exercise, respectively. Therefore, subjects with obesity seem to display a suboptimal physiological response to acute exercise stimuli. It might be hypothesized that hormonal disturbances contribute, at least in part, to these abnormal physiological reactions in the obese. This review discusses the impact of acute endurance and resistance exercise on endocrine hormones directly related to lipolysis and/or skeletal muscle protein synthesis (insulin, [nor]epinephrine, cortisol, growth hormone, testosterone, triiodothyronine, atrial natriuretic peptide, insulin-like growth factor-1), as well as the impact of long-term endurance and resistance exercise intervention on these hormonal responses to acute endurance and resistance exercise. In the obese, some endocrinological disturbances during acute endurance and resistance exercise have been identified: a blunted blood growth hormone, atrial natriuretic peptide and epinephrine release, and greater cortisol and insulin release. These hormonal disturbances might contribute to a suppressed lipolytic response, and/or suppressed skeletal muscle protein synthesis, as a result of acute endurance or resistance exercise, respectively. In subjects with obesity, the impact of acute endurance and resistance exercise on other endocrine hormones (norepinephrine, testosterone, triiodothyronine, insulin-like growth factor-1) remains elusive. Furthermore, whether long-term endurance and resistance exercise intervention might reverse these hormonal disturbances during acute endurance and resistance exercise in these individuals remains unknown.

Exercise Dose and Insulin Sensitivity

Exercise improves insulin resistance and is a first line for the prevention and treatment of type 2 diabetes. The extent, however, to which these responses are dose dependent is not known. The purpose of this study was to examine whether exercise dose was associated with improvements in insulin sensitivity after 4 months of exercise training in previously sedentary adults. Fifty-five healthy volunteers participated in a 16-wk supervised endurance exercise intervention with a pre/postintervention design. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp, peak oxygen uptake by a graded exercise test, and body composition by dual-energy x-ray absorptiometry. The exercise intervention consisted of three to five sessions per week with a minimum of three sessions supervised. A ramped exercise prescription protocol was used to achieve 75% of peak HR for 45 min per session. Exercise dose, expressed as average kilocalories expended per week, was computed as the product of exercise intensity, duration and frequency. Improved insulin sensitivity was significantly related to exercise dose in a graded dose-response relationship. No evidence of threshold or maximal dose-response effect was observed. Age and gender did not influence this dose-response relationship. Exercise intensity was also significantly related to improvements in insulin sensitivity, whereas frequency was not. This study identifies a graded dose-response relationship between exercise dose and improvements in insulin sensitivity. The implication of this observation is of importance for the adaptation of exercise prescription in clinical situations.

Alpe d’HuZes Cancer Rehabilitation (A-CaRe) Research: Four Randomized Controlled Exercise Trials and Economic Evaluations in Cancer Patients and Survivors

BackgroundPrevious studies showed that exercise in cancer patients is feasible and may reduce fatigue and improve physical fitness and quality of life. However, many previous studies had methodological weaknesses related to trial design, sample size, comparison group, outcome measures, short follow-up durations and programme content.PurposeThis paper aims to present the rationale and design of the clinical research subprogramme of the Alpe d’HuZes Cancer Rehabilitation (A-CaRe) programme.MethodA-CaRe Clinical Research includes four randomized controlled trials in patients: (a) after chemotherapy, (b) during chemotherapy, (c) after stem cell transplantation and (d) during childhood cancer. These trials compare high-intensity resistance and endurance exercise interventions with usual care or a waiting list control group. In two studies, a second intervention arm consisting of low-to-moderate intensity exercise is included. All four A-CaRe trials use similar methods.ResultsOutcome measures are carefully chosen based on the International Classification of Functioning Disability and Health model. Measurements will be performed prior to randomization (T0), after completion of the intervention (T1) and at follow-up (T2). The primary outcome measures are cardiorespiratory fitness, muscle strength and fatigue. Secondary outcome measures include health-related quality of life and psychosocial functioning. Furthermore, cost-effectiveness and cost-utility analyses are performed from a societal perspective.ConclusionWe hypothesize that exercise is more effective at improving physical fitness and thereby reducing fatigue and more cost-effective compared with usual care or a waiting list control group. If so, the programmes will be implemented in the Dutch clinical practice.

The effect of endurance exercise on the power, speed, talent and anaerobic capacities of teenage female basketball players

The aim of this study is to investigate a 16-week endurance exercise in terms of power, speed, ability and aerobic capacity in 13–16-year-old female basketball players. Twenty female basketball players...

Impact of a mixed strength and endurance exercise intervention on levels of adiponectin, high molecular weight adiponectin and leptin in breast cancer survivors

Evidence suggests that exercise affects breast cancer risk and outcomes, but little is known about the mechanisms through which this effect may be mediated. This study examines the impact of exercise upon levels of adiponectin, high molecular weight adiponectin (HMWA), and leptin in breast cancer survivors. One hundred and one sedentary, overweight breast cancer survivors were randomized to a 16-week exercise intervention or usual care control group. Anthropometric measurements were taken and fasting levels of adiponectin, HMWA and leptin were collected at baseline and 16 weeks. Baseline and week-16 measurements were available for 81 patients. The exercise group experienced a significant decrease in hip measurements, with no change in weight or body composition. There were no significant changes in adiponectin, HMWA, or leptin in either group. Modeling analyses demonstrated a significant inverse relationship between changes in leptin and adiponectin, but no relationship between changes in BMI, waist or hip circumference, or body fat percentage and change in leptin or adiponectin. This study did not demonstrate a significant change in adipocytokine levels in breast cancer survivors participating in an exercise intervention, suggesting that further work is needed to explore the mechanisms through which exercise may impact breast cancer.

Impact of a Mixed Strength and Endurance Exercise Intervention on Insulin Levels in Breast Cancer Survivors

Accumulating data suggest that exercise may affect breast cancer risk and outcomes. Studies have demonstrated that high levels of insulin, often seen in sedentary individuals, are associated with increased risk of breast cancer recurrence and death. We sought to analyze whether exercise lowered insulin concentrations in breast cancer survivors. One hundred one sedentary, overweight breast cancer survivors were randomly assigned either to a 16-week cardiovascular and strength training exercise intervention or to a usual care control group. Fasting insulin and glucose levels, weight, body composition, and circumference at the waist and hip were collected at baseline and 16 weeks. Baseline and 16-week measurements were available for 82 patients. Fasting insulin concentrations decreased by an average of 2.86 microU/mL in the exercise group (P = .03), with no significant change in the control group (decrease of 0.27 microU/mL, P = .65). The change in insulin levels in the exercise group seemed greater than the change in controls, but the comparison did not reach statistical significance (P = .07). There was a trend toward improvement in insulin resistance in the exercise group (P = .09) but no change in fasting glucose levels. The exercise group also experienced a significant decrease in hip measurements, with no change in weight or body composition. Participation in an exercise intervention was associated with a significant decrease in insulin levels and hip circumference in breast cancer survivors. The relationship between physical activity and breast cancer prognosis may be mediated, in part, through changes in insulin levels and/or changes in body fat or fat deposition.

Insulin in the Adjuvant Breast Cancer Setting: A Novel Therapeutic Target for Lifestyle and Pharmacologic Interventions?

Insulin in the Adjuvant Breast Cancer Setting: A Novel Therapeutic Target for Lifestyle and Pharmacologic Interventions?

NFKB1 promoter variation implicates shear-induced NOS3 gene expression and endothelial function in prehypertensives and stage I hypertensives

In endothelial cells, NF-kappaB is an important intracellular signaling molecule by which changes in wall shear stress are transduced into the nucleus to initiate downstream endothelial nitric oxide synthase (NOS3) gene expression. We investigated whether NF-kappa light-chain gene enhancer in B cells 1 (NFKB1) promoter polymorphism ((-94)NFKB1 I/D, where I is the insertion allele and D is the deletion allele) was associated with 1) NOS3 gene expression in endothelial cells under physiological levels of unidirectional laminar shear stress (LSS) and 2) endothelial function in prehypertensive and stage I hypertensive individuals before and after a 6-mo supervised endurance exercise intervention. Competitive EMSAs revealed that proteins present in the nuclei of endothelial cells preferentially bound to the I allele NFKB1 promoter compared with the D allele. Reporter gene assays showed that the I allele promoter had significantly higher activity than the D allele. In agreement with these observations, homozygous II genotype cells had higher p50 expression levels than homozygous DD genotype cells. Cells with the homozygous II genotype showed a greater increase in NOS3 protein expression than did homozygous DD genotype cells under LSS. Functional experiments on volunteers confirmed higher baseline reactive hyperemic forearm blood flow, and, furthermore, the subgroup analysis revealed that DD homozygotes were significantly less prevalent in the exercise responder group compared with II and ID genotypes. We conclude that the (-94)NFKB1 I/D promoter variation contributes to the modulation of vascular function and adaptability to exercise-induced flow shear stress, most likely due to differences in NFKB1 gene transactivity.