Biomedical subjects

Charles J Tanner

Publications and source records attributed to Charles J Tanner.

13 recordsLinked to original sources

PubMed2006

Response of high-sensitivity C-reactive protein to exercise training in an at-risk population.

BACKGROUND: High-sensitivity C-reactive protein (hsCRP) is promoted as an independent predictor of atherosclerotic risk. In addition, cardiorespiratory fitness is inversely related to hsCRP in single-sex cross-sectional analyses. Our objective was to determine if modulating fitness with exercise training imposes changes in high-sensitivity C-reactive protein in a mixed-sex population at risk for cardiovascular disease. METHODS: We studied baseline and postintervention plasma hsCRP in 193 sedentary, overweight to mildly obese, dyslipidemic men and women who were randomized to 6 months of inactivity or 1 of 3 aerobic exercise groups: low amount-moderate intensity (energy equivalent of approximately 19.3 km/wk at 40%-55% peak VO2), low amount-high intensity (energy equivalent of approximately 19.3 km/wk at 65%-80% peak VO2), or high amount-high intensity (energy equivalent of approximately 32.2 km/wk at 65%-80% peak VO2). RESULTS: At baseline, the study population was at intermediate to high cardiovascular risk as defined by hsCRP. Cardiorespiratory fitness was inversely related to hsCRP (P < .001) even after adjusting for significant and expected sex differences. Fitness, hormone replacement therapy use, and high-density lipoprotein cholesterol accounted for the sex difference in baseline hsCRP. Fitness, high-density lipoprotein cholesterol, fasting insulin, hormone replacement therapy, and visceral adiposity were all independent predictors for baseline hsCRP (r2 = 0.34 for the entire model, P < .0001). However, despite significant improvements in fitness, visceral adiposity, subcutaneous adiposity, and insulin sensitivity, hsCRP did not change in response to exercise training (P > .20). CONCLUSIONS: Cardiorespiratory fitness is inversely related to hsCRP independent of sex and accounts for most of the large sex disparity in hsCRP. Nonetheless, in the absence of a significant change in diet, 6 months of aerobic exercise training does not produce a significant change in hsCRP in an at-risk population.

Adult↗

PubMed2006

L-citrulline reduces time to exhaustion and insulin response to a graded exercise test.

PURPOSE: Oral L-arginine supplementation has been shown to improve treadmill time to exhaustion and resting insulin sensitivity in individuals with peripheral vascular disease and type 2 diabetes, respectively. Furthermore, L-citrulline supplementation increases plasma L-arginine concentration to a level higher than that achieved by oral L-arginine supplementation. The purpose of this investigation was therefore to determine whether time to exhaustion during a graded treadmill test, as well as plasma insulin and glucose profiles, could be improved with oral L-citrulline supplementation in healthy individuals. METHODS: Seventeen young (18-34 yr), healthy male and female volunteers performed incremental treadmill tests to exhaustion following either placebo or citrulline ingestion (3 g 3 h before test, or 9 g over 24 h prior to testing). RESULTS: Steady-state submaximal respiratory exchange ratio and VO2max were not significantly different between placebo and citrulline trials. Treadmill time to exhaustion was lower following citrulline ingestion than during placebo trials (888.2 +/- 17.7 vs 895.4 +/- 17.9 s; P < 0.05; N = 17), which was accompanied by a higher rating of perceived exertion during exercise in the L-citrulline compared with the placebo condition. There was also an increase in plasma insulin in response to this high-intensity exercise in the placebo, but not in the L-citrulline, condition (P < 0.05). CONCLUSIONS: It can be concluded that, contrary to the hypothesized improvement in treadmill time following L-citrulline ingestion, there is a reduction in treadmill time following L-citrulline ingestion over the 24 h prior to testing. The normal response of increased plasma insulin following high-intensity exercise is also not present in the L-citrulline condition, indicating that L-citrulline ingestion may reduce nitric oxide-mediated pancreatic insulin secretion or increased insulin clearance.

Adolescent↗

PubMed2005

Inactivity, exercise, and visceral fat. STRRIDE: a randomized, controlled study of exercise intensity and amount.

Despite the importance of randomized, dose-response studies for proper evaluation of effective clinical interventions, there have been no dose-response studies on the effects of exercise amount on abdominal obesity, a major risk factor for metabolic syndrome, diabetes, and cardiovascular disease. One hundred seventy-five sedentary, overweight men and women with mild to moderate dyslipidemia were randomly assigned to participate for 6 mo in a control group or for approximately 8 mo in one of three exercise groups: 1) low amount, moderate intensity, equivalent to walking 12 miles/wk (19.2 km) at 40-55% of peak oxygen consumption; 2) low amount, vigorous intensity, equivalent to jogging 12 miles/wk at 65-80% of peak oxygen consumption; or 3) high amount, vigorous intensity, equivalent to jogging 20 miles/wk (32.0 km). Computed tomography scans were analyzed for abdominal fat. Controls gained visceral fat (8.6 +/- 17.2%; P = 0.001). The equivalent of 11 miles of exercise per week, at either intensity, prevented significant accumulation of visceral fat. The highest amount of exercise resulted in decreased visceral (-6.9 +/- 20.8%; P = 0.038) and subcutaneous (-7.0 +/- 10.8%; P < 0.001) abdominal fat. Significant gains in visceral fat over only 6 mo emphasize the high cost of continued inactivity. A modest exercise program, consistent with recommendations from the Centers for Disease Control/American College of Sports Medicine (CDC/ACSM), prevented significant increases in visceral fat. Importantly, a modest increase over the CDC/ACSM exercise recommendations resulted in significant decreases in visceral, subcutaneous, and total abdominal fat without changes in caloric intake.

Abdominal Fat↗

PubMed2005

Analysis of insulin-stimulated insulin receptor activation and glucose transport in cultured skeletal muscle cells from obese subjects.

Obesity is associated with impaired insulin-stimulated glucose disposal in the skeletal muscle, but whether this is an intrinsic or acquired factor is unknown. In many patients with type 2 diabetes mellitus (T2D) and their nondiabetic relatives, who have a genetic predisposition for diabetes, insulin resistance is maintained in cultured muscle cells. To study the association of obesity with defects in insulin action, we investigated insulin stimulation of both insulin receptor (IR) autophosphorylation and subsequent glucose transport in primary skeletal muscle cell cultures obtained from both nonobese and obese nondiabetic subjects. In these 2 groups, there was no difference in the ability of insulin to induce autophosphorylation of the IR, phosphorylation of the downstream serine kinase Akt/PKB, or stimulation of glucose transport. Moreover, there were no major differences in cultured muscle cell content of either the IR, the IR antagonist PC-1, or GLUT 1 and GLUT 4. These data therefore indicate that the insulin resistance associated with obesity is not maintained in cultured muscle cells and suggest that this insulin resistance is an acquired feature of obesity.

Adult↗

PubMed2005

Glucose uptake in muscle cell cultures from endurance-trained men.

PURPOSE: To examine noninsulin- (basal) and insulin-mediated glucose uptake in human skeletal muscle cells from endurance-trained and sedentary individuals. METHODS: Muscle biopsies (vastus lateralis) were obtained from competitive, endurance-trained athletes (N=12; VO2peak 64.9+/-2.3 mL.kg-1.min-1) and their sedentary counterparts (N=8; VO2peak 51.8+/-2.2 mL.kg-1.min-1), and isolated satellite cells allowed to proceed to myotubes. RESULTS: The myotubes exhibited a dose response for glucose uptake with increasing insulin concentrations; maximal glucose uptake was approximately 1.5-fold over basal. In relation to exercise training status, basal glucose uptake was significantly (P<0.05) elevated by approximately 75% in the endurance-trained versus sedentary men (20.1+/-2.1 vs 11.9+/-1.9 pmol.mg protein-1.min-1, respectively). This difference persisted at insulin concentrations of 10 and 1000 etaM, although the relative increase in insulin-mediated glucose uptake (fold increase over basal) did not differ between the sedentary and endurance-trained cells. CONCLUSIONS: These data suggest that cultured skeletal muscle cells from endurance-trained athletes may differ in respect to basal glucose uptake.

Adult↗

PubMed2005

A comparison of methods for estimating the lactate threshold.

The purpose of this study was to examine the accuracy of tests that may be used by distance runners to estimate the lactate threshold. Competitive distance runners/triathletes (N = 27) performed a criterion test that directly measured (blood lactate of 4.0 mmol.L(-1)) the lactate threshold. Subjects then performed 4 tests (VDOT, 3,200-m time trial, 30-minute time trial, Conconi) that estimate the threshold. Mean estimations of the running velocity at the lactate threshold from the 30-minute time trial (standard error of the estimate, SEE, 0.21 m.s(-1)) and VDOT (SEE 0.41 m.s(-1)) methods did not differ (P>0.05) from the criterion. In terms of heart rate, the 30-minute time trial estimation did not significantly differ (SEE 8.0 b.min(-1)) from criterion. These findings suggest that the 30-minute time-trial method should be considered by coaches and distance runners/triathletes as a method for estimating both the running velocity and heart rate at the lactate threshold.

Adult↗

PubMed2003

Effect of the volume and intensity of exercise training on insulin sensitivity.

Physical activity enhances insulin action in obese/overweight individuals. However, the exercise prescription required for the optimal enhancement is not known. The purpose of this study was to test the hypothesis that exercise training consisting of vigorous-intensity activity would enhance insulin sensitivity more substantially than moderate-intensity activity. Sedentary, overweight/obese subjects (n = 154) were randomly assigned to either control or an exercise group for 6 mo: 1) low-volume/moderate-intensity group [ approximately 12 miles walking/wk at 40-55% peak O2 consumption (Vo2 peak)], 2) low-volume/high-intensity group ( approximately 12 miles jogging/wk at 65-80% Vo2 peak), and 3) high-volume/high-intensity group ( approximately 20 miles jogging/wk at 65-80% Vo2 peak). Training volume (miles/wk) was achieved by exercising approximately 115 min/wk (low-volume/high-intensity group) or approximately 170 min/wk (low-volume/moderate-intensity and high-volume/high-intensity groups). Insulin action was measured with an insulin sensitivity index (SI) from an intravenous glucose tolerance test. In the control group, there was a decrement (P < 0.05) in SI. In contrast, all the exercise groups significantly (P < 0.05) increased SI; the relative increment in the low-volume/moderate-intensity and high-volume/high-intensity groups ( approximately 85%) were greater than in the low-volume/high-intensity group ( approximately 40%). In conclusion, physical activity encompassing a wide range of intensity and volume minimizes the insulin resistance that develops with a sedentary lifestyle. However, an exercise prescription that incorporated approximately 170 min of exercise/wk improved insulin sensitivity more substantially than a program utilizing approximately 115 min of exercise/wk, regardless of exercise intensity and volume. Total exercise duration should thus be considered when designing training programs with the intent of improving insulin action.

Blood Glucose↗

PubMed2002

Effect of weight loss on muscle lipid content in morbidly obese subjects.

The purpose of this study was to test the hypothesis that weight loss results in a reduction in intramuscular lipid (IMCL) content that is concomitant with enhanced insulin action. Muscle biopsies were obtained from morbidly obese individuals [body mass index (BMI) 52.2 +/- 2.5 kg/m(2); n = 6] before and after gastric bypass surgery, an intervention that improves insulin action. With intervention, there was a 47% reduction (P < 0.01) in BMI and a 93% decrease in homeostasis model assessment, or HOMA (7.0 +/- 1.9 vs. 0.5 +/- 0.1). Histochemically determined IMCL content decreased (P < 0.05) by approximately 30%. In relation to fiber type, IMCL was significantly higher in type I vs. type II fibers. In both fiber types, there were reductions in IMCL and trends for muscle atrophy. Despite these two negating factors, the IMCL-to-fiber area ratio still decreased by approximately 44% with weight loss. In conclusion, despite differing initial levels and possible atrophy, weight loss appears to decrease IMCL deposition to a similar relative extent in type I and II muscle fibers. This reduction in intramuscular triglyceride may contribute to enhanced insulin action seen with weight loss.

Adipose Tissue↗

PubMed2002

Adiponectin is not altered with exercise training despite enhanced insulin action.

Adiponectin is an adipocytokine that is hypothesized to be involved in the regulation of insulin action. The purpose of the present investigation was to determine whether plasma adiponectin is altered in conjunction with enhanced insulin action with exercise training. An insulin sensitivity index (S(I)) and fasting levels of glucose, insulin, and adiponectin were assessed before and after 6 mo of exercise training (4 days/wk for approximately 45 min at 65-80% peak O(2) consumption) with no loss of body mass (PRE, 91.9 +/- 3.8 kg vs. POST, 91.6 +/- 3.9 kg) or fat mass (PRE, 26.5 +/- 1.8 kg vs. POST, 26.7 +/- 2.2 kg). Insulin action significantly (P < 0.05) improved with exercise training (S(I) +98%); however, plasma adiponectin concentration did not change (PRE, 6.3 +/- 1.5 microg/ml vs. POST, 6.6 +/- 1.8 microg/ml). In contrast, in a separate group of subjects examined before and after weight loss, there was a substantial increase in adiponectin (+281%), which was accompanied by enhanced insulin action (S(I), +432%). These data suggest that adiponectin is not a contributory factor to the exercise-related improvements in insulin sensitivity.

Adiponectin↗

PubMed2002

Muscle fiber type is associated with obesity and weight loss.

The purpose of this study was to test the hypothesis that muscle fiber type is related to obesity. Fiber type was compared 1) in lean and obese women, 2) in Caucasian (C) and African-American (AA) women, and 3) in obese individuals who lost weight after gastric bypass surgery. When lean (body mass index 24.0 +/- 0.9 kg/m(2), n = 28) and obese (34.8 +/- 0.9 kg/m(2), n = 25) women were compared, there were significant (P < 0.05) differences in muscle fiber type. The obese women possessed fewer type I (41.5 +/- 1.8 vs. 54.6 +/- 1.8%) and more type IIb (25.1 +/- 1.5 vs. 14.4 +/- 1.5%) fibers than the lean women. When ethnicity was accounted for, the percentage of type IIb fibers in obese AA was significantly higher than in obese C (31.0 +/- 2.4% vs. 19.2 +/- 1.9%); fewer type I fibers were also found in obese AA (34.5 +/- 2.8% vs. 48.6 +/- 2.2%). These data are consistent with the higher incidence of obesity and greater weight gain reported in AA women. With weight loss intervention, there was a positive relationship (r = 0.72, P < 0.005) between the percentage of excess weight loss and the percentage of type I fibers in morbidly obese patients. These findings indicate that there is a relationship between muscle fiber type and obesity.

Adult↗

PubMed2002

Effect of short-term exercise training on insulin-stimulated PI 3-kinase activity in middle-aged men.

The purpose of this study was to determine whether the improved insulin action with short-term exercise training in middle-aged individuals is associated with enhanced phosphatidylinositol (PI) 3-kinase activity in skeletal muscle. Nine men of ages 50-70 yr were studied before and after 7 consecutive days of supervised exercise (60 min/day, 70% peak O2 consumption). Insulin sensitivity was measured with a euglycemic hyperinsulinemic glucose clamp in the sedentary condition and 15-17 h after the final exercise session. Anti-phosphotyrosine-associated PI 3-kinase activity was determined from muscle samples obtained in the fasted condition and after 60 min of insulin infusion during the clamp. With exercise, the glucose infusion rate increased (P < 0.001) by 33%, indicating enhanced insulin action (mean +/- SE, 6.6 +/- 0.6 vs. 8.7 +/- 0.8 mg x kg(-1) x min(-1)). Short-term exercise training did not, however, increase insulin-stimulated (insulin stimulated/fasting) PI 3-kinase activity (1.8 +/- 0.8 vs. 1.8 +/- 0.7-fold stimulation with insulin pre- vs. posttraining, respectively). There was also no change in insulin-stimulated protein kinase B activity (1.3 +/- 0.1 vs. 1.4 +/- 0.2-fold stimulation with insulin) with training. These data suggest that insulin action is enhanced with short-term exercise training via an adaptation distal to PI 3-kinase in middle-aged, insulin-resistant individuals.

Aged↗

PubMed2002

Effect of weight loss on insulin sensitivity and intramuscular long-chain fatty acyl-CoAs in morbidly obese subjects.

Increases in intramyocellular long-chain fatty acyl-CoAs (LCACoA) have been implicated in the pathogenesis of insulin resistance in skeletal muscle. To test this hypothesis, we measured muscle (vastus lateralis) LCACoA content and insulin action in morbidly obese patients (n = 11) before and after weight loss (gastric bypass surgery). The intervention produced significant weight loss (142.3 +/- 6.8 vs. 79.6 +/- 4.1 kg for before versus after surgery, respectively). Fasting insulin decreased by approximately 84% (23.3 +/- 3.8 vs. 3.8 +/- 0.5 mU/ml), and insulin sensitivity, as determined by minimal model, increased by approximately 360% (1.2 +/- 0.3 vs. 4.1 +/- 0.5 min(-1). [ micro U/kg(-1)]) indicating enhanced insulin action. Muscle palmityl CoA (16:0; 0.54 +/- 0.08 vs. 0.35 +/- 0.04 nmol/g wet wt) concentration decreased by approximately 35% (P < 0.05) with weight loss, whereas stearate CoA (18:0; -17%; 0.65 +/- 0.05 vs. 0.54 +/- 0.03 nmol/g wet wt) and linoleate CoA (18:2; -30%; 2.47 +/- 0.27 vs. 1.66 +/- 0.19 nmol/g wet wt) were also reduced (P < 0.05). There were no statistically significant declines in muscle palmitoleate CoA (16:1), oleate CoA (18:1), or total LCACoA content. These data suggest that a reduction in intramuscular LCACoA content may be responsible, at least in part, for the enhanced insulin action observed with weight loss in obese individuals.

Adult↗

PubMed2002

Peroxisome proliferator-activated receptor-alpha regulates fatty acid utilization in primary human skeletal muscle cells.

In humans, skeletal muscle is a major site of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) expression, but its function in this tissue is unclear. We investigated the role of hPPAR-alpha in regulating muscle lipid utilization by studying the effects of a highly selective PPAR-alpha agonist, GW7647, on [(14)C]oleate metabolism and gene expression in primary human skeletal muscle cells. Robust induction of PPAR-alpha protein expression occurred during muscle cell differentiation and corresponded with differentiation-dependent increases in oleate oxidation. In mature myotubes, 48-h treatment with 10-1,000 nmol/l GW7647 increased oleate oxidation dose-dependently, up to threefold. Additionally, GW7647 decreased oleate esterification into myotube triacylglycerol (TAG), up to 45%. This effect was not abolished by etomoxir, a potent inhibitor of beta-oxidation, indicating that PPAR-alpha-mediated TAG depletion does not depend on reciprocal changes in fatty acid catabolism. Consistent with its metabolic actions, GW7647 induced mRNA expression of mitochondrial enzymes that promote fatty acid catabolism; carnitine palmityltransferase 1 and malonyl-CoA decarboxylase increased approximately 2-fold, whereas pyruvate dehydrogenase kinase 4 increased 45-fold. Expression of several genes that regulate glycerolipid synthesis was not changed by GW7647 treatment, implicating involvement of other targets to explain the TAG-depleting effect of the compound. These results demonstrate a role for hPPAR-alpha in regulating muscle lipid homeostasis.

Butyrates↗