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Biomedical subjects

W M Sherman

Publications and source records attributed to W M Sherman.

At least 55 records · Page 3Linked to original sources

Training-induced vascular and metabolic adaptations in normo(11 week)- and hyper(18 week)-glycemic obese Zucker rats.

The purpose of this study was to investigate the peripheral vascular and metabolic adaptations induced by aerobic training in normoglycemic (11-week-old) and hyperglycemic (18-week-old) insulin-resistant male obese Zucker rats (OZR). OZR were treadmill trained 6-11 (T6-11), 11-18 (T11-18), or 6-18 (T6-18) weeks of age at 15 m/min. 17 percent grade, 1 hour/day, 5 days/week. Forty-eight hours after the last training session and after a 12 hour fast, a tail vein blood sample was obtained for analysis of glucose and insulin concentrations, cholesterol, and glycosylated hemoglobin fraction. Glucose uptake and hindlimb vascular resistance were measured during extracorporeal perfusion of the hindlimb (1.0mU insulin/ml). Trained animals were compared to sedentary age-matched obese (S-OZR) and lean (LZR) animals. S-OZR were hyperinsulinemic and obese at 6 weeks of age, mildly hypercholesterolemic and hyperglycemic at 11 weeks, and profoundly hyperglycemic at 18 weeks. Training did not affect body weight or serum cholesterol. Fasting insulin and glucose concentrations were not different between sedentary and trained OZR, except T6-18 which had higher insulin and lower glucose concentrations. The insulin/glucose ratio was lower in OZR animals and was not altered by 6-7 week training (T6-11, T11-18), but was normalized by 12 week training (T6-18). No significant differences in glycosylated hemoglobin fractions were observed between groups. Normalization of glucose uptake was observed in trained 11-week-old OZR, and a statistically non-significant (P = 0.10) 40 percent improvement was observed in trained 18-week-old OZR. Hindlimb vascular resistance was elevated in the S-OZR, relative to LZR, at 11 and 18 weeks of age, and was reduced with training. One hour/day exercise training normalized hindlimb vascular resistance and glucose uptake in 11-week-old OZR, but only moderately improves these vascular and metabolic variables in 18-week-old hyperglycemic animals. Prolonged (12 weeks) training reduced the severity of fasting hyperglycemia in older animals, but at the expense of an increased fasting insulin concentration.

Adaptation, Physiological↗

Effects of 4 h preexercise carbohydrate feedings on cycling performance.

This study determined the effects of consuming three different amounts of liquid carbohydrate 4 h before exercise on the metabolic responses during exercise and on exercise performance. Four hours before exercise subjects consumed either 45 (L) or 156 (M) g of carbohydrate in isocaloric feedings and either 0 (P) or 312 (H) g of carbohydrate. Interval cycling was undertaken for 95 min, followed by a performance trial. Blood glucose had reached basal 1 h after all feedings; blood insulin had reached basal 3 h after ingestion of P, L, and M but was still 84% higher for H at the start of exercise. During exercise insulin averaged 48% higher for H than P. Blood glucose decreased 16% during exercise for P, L, and M, whereas for H there was a transient drop the first 15 min of exercise, after which glucose increased and remained constant throughout exercise. More carbohydrate oxidation occurred during exercise for H vs P, whereas results were similar for L and M. Ingestion of H improved performance by 15% as compared with P, whereas performance was similar for L and M. These results indicate that, despite elevated insulin at the start of and during exercise, consumption of 312 g of carbohydrate 4 h before moderately intense prolonged exercise can improve performance, perhaps via an enhancement of carbohydrate oxidation.

Adult↗

Glucose transport: locus of muscle insulin resistance in obese Zucker rats.

The purposes of this study were to determine whether the muscle insulin resistance of the obese rat is due to a defect in the glucose transport process and whether the insulin resistance is fiber-type specific. The hindlimbs of fasted, 14-wk-old obese (fa/fa) and lean (fa/?) Zucker rats were perfused with perfusate containing 8 mM glucose and no insulin or 8 mM glucose and either a physiological (0.15 mU/ml), a submaximal (1.50 mU/ml), or a maximal (15.0 mU/ml) insulin concentration. Glucose uptake was determined after which the initial rate of glucose transport was determined using 3-O-methyl-D-glucose (3-OMG). Glucose uptake of the obese rats was depressed by 40, 33, 42, and 47% in the absence of insulin and in the presence of the physiological, submaximal, and maximal insulin concentrations, respectively, when compared with lean littermates. Glucose transport in the absence and in the presence of the three insulin concentrations was significantly lower in the soleus (slow-twitch, oxidative fibers), red quadriceps (fast-twitch, oxidative, glycolytic fibers), and gastrocnemius (mixed fibers) of the obese rats when compared with lean rats. Glucose transport in the white quadriceps (fast-twitch, glycolytic fibers) was significantly lower in the obese rats in the absence of insulin and in the presence of the submaximal and maximal insulin concentrations. The glycogen concentration and the activity of hexokinase were the same and the glycogen synthase activity was higher in the muscles for the obese rats when compared to lean rats.(ABSTRACT TRUNCATED AT 250 WORDS)

3-O-Methylglucose↗

Muscle glycogen synthesis after exercise: effect of time of carbohydrate ingestion.

The time of ingestion of a carbohydrate supplement on muscle glycogen storage postexercise was examined. Twelve male cyclists exercised continuously for 70 min on a cycle ergometer at 68% VO2max, interrupted by six 2-min intervals at 88% VO2max, on two separate occasions. A 25% carbohydrate solution (2 g/kg body wt) was ingested immediately postexercise (P-EX) or 2 h postexercise (2P-EX). Muscle biopsies were taken from the vastus lateralis at 0, 2, and 4 h postexercise. Blood samples were obtained from an antecubital vein before and during exercise and at specific times after exercise. Muscle glycogen immediately postexercise was not significantly different for the P-EX and 2P-EX treatments. During the first 2 h postexercise, the rate of muscle glycogen storage was 7.7 mumol.g wet wt-1.h-1 for the P-EX treatment, but only 2.5 mumol.g wet wt-1.h-1 for the 2P-EX treatment. During the second 2 h of recovery, the rate of glycogen storage slowed to 4.3 mumol.g wet wt-1.h-1 during treatment P-EX but increased to 4.1 mumol.g wet wt-1.h-1 during treatment 2P-EX. This rate, however, was still 45% slower (P less than 0.05) than that for the P-EX treatment during the first 2 h of recovery. This slower rate of glycogen storage occurred despite significantly elevated plasma glucose and insulin levels. The results suggest that delaying the ingestion of a carbohydrate supplement post-exercise will result in a reduced rate of muscle glycogen storage.

Adult↗

Exercise modality and selected coronary risk factors: a multivariate approach.

To evaluate group differences in coronary risk which could be attributed to the modality of habitual exercise, selected physiologic and lipid indices of coronary artery disease (CAD) were measured in 57 endurance trained (ET), strength trained (ST), or sedentary (SED) men (19 per group, aged 21 to 44 yr). Initial data reduction accomplished with principle component analysis identified three factors with eigenvalues greater than one. Orthogonal rotation of the preliminary solution demonstrated that low density lipoprotein cholesterol (LDL-C), percent body fat (%BF) and VO2max, and high density lipoprotein cholesterol (HDL-C) could be used to represent Factors 1, 2, and 3, respectively. The subsequent MANOVA using these variables proved significant. Post hoc analysis via simultaneous confidence intervals indicated that LDL-C group differences were not significant. Values for %BF and HCL-C in the ST group (14.0% and 1.17 mmol.l-1, respectively) were between but did not differ significantly from respective values in the ET (11.8% and 1.34 mmol.l-1) and SED (18.7% and 1.13 mmol.l-1) groups. However, %BF and HDL-C differences between the ET and SED groups were significant. The VO2max of the ET subjects (63.2 ml.kg-1.min-1) was significantly higher than that of either the ST or SED subjects (49.5 and 46.7 ml.kg-1.min-1, respectively). These results suggest that ET is the most effective modality of exercise for CAD risk reduction while benefits derived from ST are minimal.

Adult↗

Progressive metabolite changes in individual human muscle fibers with increasing work rates.

Muscle biopsies were obtained from vastus lateralis muscles of four volunteers exercising at increasing work rates on a bicycle ergometer. Samples were taken at rest (t1), after a work load 23% below the blood lactate threshold (t2), 23% above this threshold (t3), and at exhaustion (t4). Individual muscle fibers were typed by their lactate dehydrogenase and adenylokinase levels and assayed for lactate, glucose-6-phosphate, and malate, (which preliminary data indicated to be the most responsive to increased activity) as well as ATP and phosphocreatine. The results in three of the four cases indicated that by the time of the t2 sample, almost all fibers, regardless of type, had been recruited. Additionally, there were no major differences in lactate concentration between type 1 and 2 fibers from muscle samples taken at t1, t2, and t3. It is concluded that in a muscle with fast-twitch glycolytic and slow-twitch oxidative fibers, all fibers share in the contraction to a substantial degree, even at moderate work loads, and that both the type 1 and 2 fibers contribute significantly to the initial rise in blood lactate during a graded exercise task. Metabolite responses in type 2 fibers differed in certain respects among the four participants. This is attributed to differences in their training backgrounds and consequent differences in type 2 fiber oxidative enzyme levels.

Adenosine Triphosphate↗

Exercise and diet reduce muscle insulin resistance in obese Zucker rat.

Two treatments that increase skeletal muscle insulin action are exercise training and high-carbohydrate diet. The purpose of the present study was to determine whether exercise training and a diet high in carbohydrates could function synergistically to reduce the muscle insulin resistance in the obese Zucker rat. Obese rats 4 wk of age were randomly assigned to an exercise or sedentary group. Each group was subdivided by diet with one-half of the rats fed a high-carbohydrate diet and one-half fed a high-fat diet. Lean Zucker rats fed the high-fat diet were used as controls. Muscle insulin resistance was assessed during hindlimb perfusion with a submaximally stimulating concentration of insulin. Exercise training and the high-carbohydrate diet increased the rate of muscle glucose uptake in the obese rat by 46 and 53%, respectively. More importantly, the combined effect of exercise training and high-carbohydrate diet was greater than the sum of their individual effects. Glycogen synthesis paralleled glucose uptake and was the major pathway for intracellular glucose disposal. Muscle glucose uptake for exercise-trained, high-carbohydrate fed obese rats was comparable with that of lean controls. It is concluded that exercise training and the high-carbohydrate diet functioned synergistically to reduce the muscle insulin resistance in the obese rat.

Animals↗

Influence of dietary carbohydrate on skeletal muscle glucose uptake.

The effect of altering the percent of dietary carbohydrate on the rate of skeletal muscle glucose uptake was studied using the perfused rat hindlimb preparation. The rats received either a high carbohydrate (HC; 65%), mixed (M; 35%) or low carbohydrate (LC; 10%) isocaloric diet for 7 days. With 0.1 mU/ml of insulin in the perfusate, the muscle of rats on the HC diet had a 33% increase in the rate of glucose uptake and the muscle of rats fed the LC diet a 23% decrease in the rate of glucose uptake when compared to the muscle of rats fed the M diet (3.34 mumol/g/30 min). With 10.0 mU/ml of insulin in the perfusate, ie maximal insulin stimulation, the rate of glucose uptake showed a similar dietary effect as that obtained with 0.1 mU/ml insulin. Compared to the M diet (8.67 mumol/g/30 min), the rate of glucose uptake increased 26% in muscle of rats from the HC group and decreased by 20% in muscle of rats from the LC group. Diet had no effect on the rate of muscle glucose uptake in the absence of insulin. Under both maximal and submaximal insulin stimulation, glycogen accumulation was greatest in muscle from HC fed rats and least in muscle from LC fed rats. During perfusion muscle intracellular free glucose and glucose-6-phosphate accumulation for the three dietary groups was negligible. The groups did not differ significantly in their muscle hexokinase or beta-hydroxyl acyl CoA dehydrogenase activities.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxyacyl CoA Dehydrogenases↗

Creatine kinase-MB isoenzyme adaptations in stressed human skeletal muscle of marathon runners.

The creatine kinase (CK) isoenzyme composition was determined in serial gastrocnemius muscle biopsies obtained from 12 male marathon runners. The mean muscle CK-MB composition significantly increased after chronic exercise (training) from 5.3% (pretraining) to 7.7% (premarathon) as well as after acute exercise (postmarathon) to 10.5% of the total CK activity (P less than 0.05). However, no significant differences in total CK activities were detected. Additionally, mitochondrial CK and CK-BB isoenzymes were present in muscle homogenates. A significant correlation was observed in the increase in mean serum total CK (3,322 U/l) and CK-MB (174 U/l) activities 24 h after the race (r = 0.98, P less than 0.05). These results show that gastrocnemius muscle adapts to long-distance training and racing with increased CK-MB activities and imply that skeletal muscle is the major source of elevated serum CK-MB activities in marathon runners.

Adaptation, Physiological↗

Effects of elevated and exercise-reduced muscle glycogen levels on insulin sensitivity.

The effects of an exercise-induced muscle glycogen reduction and an elevated muscle glycogen concentration on glucose tolerance and the insulin response to an oral glucose tolerance test (GTT) were examined. GTTs were administered to seven male subjects after 3 days on a mixed diet (C), after exhaustive exercise and 1 day on a high-fat protein diet (L-FP), after exhaustive exercise and 1 day on a mixed diet (L-M), and after exhaustive exercise and 3 days on a high-carbohydrate diet (H-CHO). The L-M treatment resulted in a significant reduction in muscle glycogen (C, 79.6 +/- 4.2 mmol/kg wet wt vs. L-M, 53.9 +/- 1.2 mmol/kg wet wt) and a 31.7% reduction in the insulin-glucose (IG) index, a measure of insulin sensitivity in vivo. Muscle glycogen was also significantly reduced by the L-FP treatment (49.1 +/- 2.4 mmol/kg wet wt), but there was no change in the IG index. Preventing a decrease in the IG index during the L-FP treatment may have been a result of elevated free fatty acids (67%) and ketones (552%) prior to the GTT. Muscle glycogen was significantly increased by the H-CHO treatment (124.8 +/- 11.1 mmol/kg wet wt); however, the IG index was not different from that of the C treatment. The results suggest that an exercise-induced reduction in muscle glycogen can improve insulin sensitivity in vivo but that this effect is diet dependent.

Adult↗

Comparison of serum creatine kinase and creatine kinase MB activities post marathon race versus post myocardial infarction.

Serial total creatine kinase (CK) and CK MB activities were determined in the serum of seven runners following a marathon race and compared to enzyme activities in the sera from five patients following acute myocardial infarction (AMI). In the runner's sera, total CK and CK MB activities were significantly elevated at 1, 24, 48 and 72 hours post marathon race when compared to the 1 hour pre-marathon samples (p less than 0.01). Serum CK MB activities peaked at 24 hours in both groups of subjects. The MB activities 24 hours following the marathon were substantially higher (91 +/- 30 U/l; mean +/- SD) than the MB activities 24 hours following AMI (46 +/- 38 U/l). However, the percentages of CK MB 24 hours following the marathon and AMI were almost identical (7.0 +/- 2.4% and 7.2 +/- 2.3%, respectively). Furthermore, CK and CK MB clearances were significantly prolonged (p less than 0.02 and p less than 0.001, respectively) following the marathon race (T 1/2 CK, 49 hours; T 1/2 CK MB, 29 hours) as compared to following AMI (T 1/2 CK, 27 hours; T 1/2 CK MB, 12 hours). These results suggest release of CK MB from the skeletal muscle of marathon runners. Therefore, we recommend that elevation of CK MB in the range indicative of myocardial damage be interpreted with caution in long-distance runners.

Adult↗

Effect of a 42.2-km footrace and subsequent rest or exercise on muscular strength and work capacity.

This study 1) quantitates the effect of a 42.2-km footrace (marathon) on leg extensor strength (maximal peak torque, MPT) and work capacity (WC, measured during a leg extensor fatigue test), and 2) describes the effect of either a rest or exercise regimen for 1 wk after the marathon on the recovery of MPT and WC. Ten trained male runners performed personal records in a marathon and were then randomly assigned to either a rest or exercise-recovery group. The rest group did not train, whereas the exercise group ran 20-45 min/day at their selected intensity of exercise [50-60% maximal O2 consumption (Vo2max)] during the recovery week. MPT was measured at 1.1, 3.2, and 5.3 rad X s-1. The total work generated during a 50-contraction active extension-passive flexion fatigue test conducted at 3.2 rad X s-1 was defined as WC. Reports of perceived soreness of the quadriceps were obtained before each strength-testing session. These measurements were obtained before the marathon and 15-20 min and 1, 3, 5, and 7 days postmarathon. A significant reduction in MPT and WC resulted and continued 1 day postmarathon. MPT of both groups improved through day 5 postmarathon at 1.1 and 3.2 rad X s-1. MPT of the rest group improved through day 7 postmarathon but remained less than premarathon MPT. Recovery of MPT was impaired in the exercise group through days 5-7 postmarathon after 40-45 min exercise at 60% Vo2max. WC was recovered 3 days postmarathon in the rest group but was still impaired 7 days postmarathon in the exercise group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of strength training on glucose tolerance and post-glucose insulin response.

The effect of muscle strength training on glucose tolerance and the insulin response after glucose feeding was investigated in eight healthy male subjects. Glucose tolerance and the associated insulin response was assessed using a standard 100-g oral glucose load before and after a supervised 10-wk high-resistance, isotonic weight-lifting program. Blood samples were drawn before and at 30, 60, 90, 120, and 150 min after ingestion of glucose. Areas under the glucose and insulin curves were used to determine differences between treatments. Muscle strength training increased body weight 3.7% and lean body mass by 3.5%, but had no effect on fat mass as determined by hydrostatic weighing. Glucose tolerance was not changed by the training program. However, a significant reduction in the basal plasma insulin concentration (37.5%) and the area under the insulin response curve (18.0%) was found (P less than 0.05). This reduction in the insulin response was significantly correlated (r = 0.89; P less than 0.05) with the increase in lean body mass. These results suggest that the increased muscle mass resulting from strength training was responsible for the attenuated insulin response to a standard 100-g oral glucose challenge.

Blood Glucose↗

Profile of creatine kinase isoenzymes in skeletal muscles of marathon runners.

The proportion of creatine kinase (CK; EC 2.7.3.2) isoenzyme MB activity was increased in skeletal muscle biopsies obtained from five long-distance runners, both 2 h before (mean 7.7%, SD 2.4%) and 30 min after (mean 7.2%, SD 1.2%) a marathon race, as compared with that in biopsies from five nonrunners (controls less than or equal to 1.0%). Further, mitochondrial CK and CK-BB isoenzymes were present in homogenates of the runners' skeletal muscle samples but not in those of the nonrunners. However, there were no substantial differences in the mean total CK activities per gram (wet wt.) of muscle tissue among premarathon samples, postmarathon samples, and nonrunners' samples (3148, 3365, and 3049 U/g, respectively). We conclude that the metabolically active gastrocnemius muscle of long-distance runners is qualitatively similar to the heart muscle in its CK isoenzyme composition.

Adult↗

Muscle fiber necrosis associated with human marathon runners.

This study describes the events occurring in exercise-induced muscular necrosis. Biopsies of the gastrocnemius muscles of volunteer human marathon runners were extracted prior to and at intervals for 7 days following a marathon, and investigated ultrastructurally. Most of the preparations, including the pre-marathon samples, showed evidence of muscle fiber necrosis and inflammation. These preparations had many mitochondria, erythrocytes, leukocytes and other phagocytic cells within the extracellular and extravascular spaces. Less frequently observed were Z-line streaming and degeneration, contracture knots, disrupted sarcolemma, presence of erythrocytes within the muscle fibers, and empty basal lamina tubes in which the contents of the fibers and the sarcolemma had broken down to leave only the basal lamina outlining the former fiber. These abnormal conditions were most prevalent at 1 and 3 days after the marathon. These ultrastructural changes are compared and correlated with the reports of clinical manifestations of rhabdomyolysis and myoglobinuria. Because the abnormalities persist for the 7 day duration of these observations, and because many of these were observed in the pre-marathon biopsies, we conclude that both the intensive training for, and the marathon itself, induce inflammation and fiber necrosis which are manifested in the clinical symptoms for rhabdomyolysis and myoglobinuria. The inflammatory reaction that accompanies these activities may be a major factor in post-exercise soreness. The combined influences of training and necrosis are discussed in relation to muscle fiber type compositions of endurance athletes.

Humans↗

Increases in HDL-cholesterol and the HDL/LDL cholesterol ratio during prolonged endurance exercise.

The influence of prolonged, low-intensity exercise (45% VO2max) until exhaustion on plasma lipid levels, in particular high-density lipoprotein cholesterol (HDL-C), and the time sequence associated with changes in these blood constituents was investigated in 10 trained subjects. The exercise consisted of walking on a motor-driven treadmill until exhaustion. Blood samples were drawn before, at 30 and 60 minutes after the beginning of exercise, at each hour thereafter until exhaustion, immediately before exhaustion, and after a 30-minute recovery period. At exhaustion the total cholesterol concentration was significantly elevated by 3% and rose another 3% during the recovery period. The HDL-C level was significantly elevated within two hours after the start of exercise and by exhaustion (about 4.5 hours of exercise) had risen to 52.5 +/- 2.3 mg X dL-1, which represented a 10.8% increase above the pre-exercise concentration (47.4 +/- 1.8 mg X dL-1). The HDL/LDL cholesterol ratio followed a pattern similar to that described for HDL-C. Plasma free fatty acids (FFA) also increased linearly during the exercise period but were not significantly correlated with HDL-C during exercise (r = 0.14). These results suggest that prolonged, low-intensity exercise can acutely improve the lipid profile of humans.

Adult↗

Effect of a 42.2-km footrace and subsequent rest or exercise on muscle glycogen and enzymes.

The purpose of this study was to determine the effect of running a marathon and subsequent rest or exercise during a 7-day recovery period on muscle glycogen, glycogen synthase, hexokinase, and the activity of hexose monophosphate pathway enzymes. Ten well-trained runners were randomly assigned to either a postmarathon rest or exercise group. The rest group (n = 5) performed no physical activity, whereas the exercise group ran at their highest tolerable volitional intensity for 20-45 min during the recovery period. Muscle biopsies were obtained from the gastrocnemius before and after the marathon and 1, 3, 5, and 7 days after the marathon. Muscle glycogen was supercompensated before the marathon (196 mmol glucosyl units kg wet tissue wt-1, mmol X kg-1) and was reduced to 25 mmol X kg-1 after the marathon. Seven days later it was 141 and 109 mmol X kg-1 in the rest and exercise groups, respectively. Measurement of glycogen synthase activity ratio indicated an active enzyme only immediately postmarathon, whereas measurement of glycogen synthase fractional velocity and relative velocity indicated an active enzyme immediately postmarathon and 1 day postmarathon. Hexokinase activity was significantly elevated immediately after the marathon and remained elevated through 5 days postmarathon. The activities of the hexose monophosphate pathway enzymes declined steadily during the experimental period and were significantly reduced 5 and 7 days postmarathon. Low-intensity exercise during the recovery week did not significantly differentiate the exercise group from the rest group.

Adult↗

Effect of glycerol feeding on endurance and metabolism during prolonged exercise in man.

This study evaluated the effectiveness of pre-exercise glycerol feeding in protecting against development of hypoglycemia and sparing muscle glycogen during prolonged, intense exercise. Thirty minutes after ingesting either glycerol (1 gm X kg-1 body weight) or a placebo, 10 cyclists performed as much exercise on a cycle ergometer as they were able in 150 min. The average exercise intensity was 72% of VO2max during both trials. Glycerol ingestion increased blood glycerol concentration 100-fold, but did not alter the respiratory exchange ratio (R), plasma levels of insulin and free-fatty acids, or blood lactate and beta-hydroxybutyrate. The only significant effect of glycerol feeding was to postpone the decline in blood glucose by about 30 min. This suggests that glycerol served, to a limited extent, as a gluconeogenic substrate; however, glycerol ingestion did not spare muscle glycogen during 90 min of treadmill exercise at 71% VO2max. It appears that man cannot utilize glycerol as gluconeogenic substrate rapidly enough to serve as a major energy source during strenuous exercise.

Administration, Oral↗