Glucose clearance in aged trained skeletal muscle during maximal insulin with superimposed exercise.

Insulin and muscle contractions are major stimuli for glucose uptake in skeletal muscle and have in young healthy people been shown to be additive. We studied the effect of superimposed exercise during a maximal insulin stimulus on glucose uptake and clearance in trained (T) (1-legged bicycle training, 30 min/day, 6 days/wk for 10 wk at approximately 70% of maximal O(2) uptake) and untrained (UT) legs of healthy men (H) [n = 6, age 60 +/- 2 (SE) yr] and patients with Type 2 diabetes mellitus (DM) (n = 4, age 56 +/- 3 yr) during a hyperinsulinemic ( approximately 16,000 pmol/l), isoglycemic clamp with a final 30 min of superimposed two-legged exercise at 70% of individual maximal heart rate. With superimposed exercise, leg glucose extraction decreased (P < 0.05), and leg blood flow and leg glucose clearance increased (P < 0.05), compared with hyperinsulinemia alone. During exercise, leg blood flow was similar in both groups of subjects and between T and UT legs, whereas glucose extraction was always higher (P < 0.05) in T compared with UT legs (15.8 +/- 1.2 vs. 14.6 +/- 1.8 and 11.9 +/- 0.8 vs. 8.8 +/- 1.8% for H and DM, respectively) and leg glucose clearance was higher in T (H: 73 +/- 8, DM: 70 +/- 10 ml. min(-1). kg leg(-1)) compared with UT (H: 63 +/- 8, DM: 45 +/- 7 ml. min(-1). kg leg(-1)) but not different between groups (P > 0.05). From these results it can be concluded that, in both diabetic and healthy aged muscle, exercise adds to a maximally insulin-stimulated glucose clearance and that glucose extraction and clearance are both enhanced by training.     

Effects of ATP-induced leg vasodilation on VO2 peak and leg O2 extraction during maximal exercise in humans

During maximal whole body exercise VO2 peak is limited by O2 delivery. In turn, it is though that blood flow at near-maximal exercise must be restrained by the sympathetic nervous system to maintain mean arterial pressure. To determine whether enhancing vasodilation across the leg results in higher O2 delivery and leg VO2 during near-maximal and maximal exercise in humans, seven men performed two maximal incremental exercise tests on the cycle ergometer. In random order, one test was performed with and one without (control exercise) infusion of ATP (8 mg in 1 ml of isotonic saline solution) into the right femoral artery at a rate of 80 microg.kg body mass-1.min-1. During near-maximal exercise (92% of VO2 peak), the infusion of ATP increased leg vascular conductance (+43%, P<0.05), leg blood flow (+20%, 1.7 l/min, P<0.05), and leg O2 delivery (+20%, 0.3 l/min, P<0.05). No effects were observed on leg or systemic VO2. Leg O2 fractional extraction was decreased from 85+/-3 (control) to 78+/-4% (ATP) in the infused leg (P<0.05), while it remained unchanged in the left leg (84+/-2 and 83+/-2%; control and ATP; n=3). ATP infusion at maximal exercise increased leg vascular conductance by 17% (P<0.05), while leg blood flow tended to be elevated by 0.8 l/min (P=0.08). However, neither systemic nor leg peak VO2 values where enhanced due to a reduction of O2 extraction from 84+/-4 to 76+/-4%, in the control and ATP conditions, respectively (P<0.05). In summary, the VO2 of the skeletal muscles of the lower extremities is not enhanced by limb vasodilation at near-maximal or maximal exercise in humans. The fact that ATP infusion resulted in a reduction of O2 extraction across the exercising leg suggests a vasodilating effect of ATP on less-active muscle fibers and other noncontracting tissues and that under normal conditions these regions are under high vasoconstrictor influence to ensure the most efficient flow distribution of the available cardiac output to the most active muscle fibers of the exercising limb.     

Endurance training has little effect on active muscle free fatty acid, lipoprotein cholesterol, or triglyceride net balances

We evaluated the hypothesis that net leg total FFA, LDL-C, and TG uptake and HDL-C release during moderate-intensity cycling exercise would be increased following endurance training. Eight sedentary men (26 +/- 1 yr, 77.4 +/- 3.7 kg) were studied in the postprandial state during 90 min of rest and 60 min of exercise twice before (45% and 65% V(O2 peak)) and twice after 9 wk of endurance training (55% and 65% posttraining V(O2 peak)). Measurements across an exercising leg were taken to be a surrogate for active skeletal muscle. To determine limb lipid exchange, femoral arterial and venous blood samples drawn simultaneously at rest and during exercise were analyzed for total and individual FFA (e.g., palmitate, oleate), LDL-C, HDL-C, and TG concentrations, and limb blood flow was determined by thermodilution. The transition from rest to exercise resulted in a shift from net leg total FFA release (-44 +/- 16 micromol/min) to uptake (193 +/- 49 micromol/min) that was unaffected by either exercise intensity or endurance training. The relative net leg release and uptake of individual FFA closely resembled their relative abundances in the plasma with approximately 21 and 41% of net leg total FFA uptake during exercise accounted for by palmitate and oleate, respectively. Endurance training resulted in significant changes in arterial concentrations of HDL-C (49 +/- 5 vs. 52 +/- 5 mg/dl, pre vs. post) and LDL-C (82 +/- 9 vs. 76 +/- 9 mg/dl, pre vs. post), but there was no net TG or LDL-C uptake or HDL-C release across the resting or active leg before or after endurance training. In conclusion, endurance training favorably affects blood lipoprotein profiles, even in young, healthy normolipidemic men, but muscle contractions per se have little effect on net leg LDL-C, or TG uptake or HDL-C release during moderate-intensity cycling exercise. Therefore, the favorable effects of physical activity on the lipid profiles of young, healthy normolipidemic men in the postprandial state are not attributable to changes in HDL-C or LDL-C exchange across active skeletal muscle.     

Effect of beta-adrenoceptor blockade on H+ and K+ flux in exercising humans

The effect of beta-adrenoceptor blockade (beta B) on muscle release and uptake of H+ and K+ in humans during maximal exercise has been investigated. Eight volunteers cycled intermittently at power outputs corresponding to 100% of maximal O2 uptake. Prior to exercise either propranolol (beta B) or saline (control) was infused into the femoral vein. Arterial and femoral venous blood samples were drawn at rest, during exercise, and during 30-min recovery. Peak arterial blood values for K+, lactic acid (LA), and base deficit (BD) (mean +/- SE) were respectively 5.5 +/- 0.1, 9.5 +/- 0.6, and 11.7 +/- 0.9 mmol/l during beta B and 5.1 +/- 0.1, 8.3 +/- 0.6, and 10.3 +/- 1.0 for control (P less than 0.05). The release of K+ from the working leg did not differ between treatments during exercise, but K+ uptake during late recovery (5-30 min) was slightly lower during beta B. Thus the higher arterial K+ levels during exercise (beta B) cannot be attributed to greater release by active muscle but are likely due to decreased K+ uptake by noncontracting muscle. Arterial-femoral venous differences for LA and BD did not differ significantly between treatments. Additionally LA exchange across the leg was similar to H+ exchange (arterial-femoral venous differences for BD) under all conditions. During early recovery (1-5 min), regardless of experimental treatment, BD levels iin arterial blood were higher than LA (P less than 0.05). These elevated BD levels may be due to unequal removal rates between LA and H+ equivalents by nonexercised tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hepatic lactate uptake versus leg lactate output during exercise in humans.

The exponential rise in blood lactate with exercise intensity may be influenced by hepatic lactate uptake. We compared muscle-derived lactate to the hepatic elimination during 2 h prolonged cycling (62 +/- 4% of maximal O(2) uptake, (.)Vo(2max)) followed by incremental exercise in seven healthy men. Hepatic blood flow was assessed by indocyanine green dye elimination and leg blood flow by thermodilution. During prolonged exercise, the hepatic glucose output was lower than the leg glucose uptake (3.8 +/- 0.5 vs. 6.5 +/- 0.6 mmol/min; mean +/- SE) and at an arterial lactate of 2.0 +/- 0.2 mM, the leg lactate output of 3.0 +/- 1.8 mmol/min was about fourfold higher than the hepatic lactate uptake (0.7 +/- 0.3 mmol/min). During incremental exercise, the hepatic glucose output was about one-third of the leg glucose uptake (2.0 +/- 0.4 vs. 6.2 +/- 1.3 mmol/min) and the arterial lactate reached 6.0 +/- 1.1 mM because the leg lactate output of 8.9 +/- 2.7 mmol/min was markedly higher than the lactate taken up by the liver (1.1 +/- 0.6 mmol/min). Compared with prolonged exercise, the hepatic lactate uptake increased during incremental exercise, but the relative hepatic lactate uptake decreased to about one-tenth of the lactate released by the legs. This drop in relative hepatic lactate extraction may contribute to the increase in arterial lactate during intense exercise.     

Effect of exercise duration on postprandial hypertriglyceridemia in men with metabolic syndrome.

We examined the effect of exercise on postprandial hypertriglyceridemia (PHTG) and insulin resistance in individuals with metabolic syndrome. Subjects were 10 hypertriglyceridemic men with insulin resistance [age = 35.0 +/- 1.8 yr, body weight = 90.7 +/- 3.3 kg, fasting triglyceride (TG) = 2.6 +/- 0.4 mmol/l, peak oxygen consumption ((.)Vo(2peak)) = 36.0 +/- 1.3 ml(-1).kg(-1).min(-1), and homeostatic model assessment of insulin resistance (HOMA-IR)= 3.1 +/- 0.3]. Each participant performed a control trial (Ctr; no exercise) and three exercise trials at 60% of their (.)Vo(2peak) for 30 min (30 min-Ex), 45 min (45 min-Ex) and 60 min (60 min-Ex). All subjects had a fat meal in each trial. In the exercise trials, the subject jogged on a treadmill for a designated duration of 12 h before ingestion of a fat meal. Blood samples were taken at 0 h (before the meal) and at 2, 4, 6, and 8 h after the meal. The plasma TG, area score under TG concentration curve over an 8-h period (TG AUC) after the meal, and HOMA-IR were analyzed. The TG AUC scores in both the 45 min-Ex and 60 min-Ex were 31 and 33% lower, respectively, than Ctr (P < 0.02). There were no significant differences in TG AUC scores between the 30 min-Ex and the Ctr (P > 0.05). There were no trial differences in the fasting plasma glucose concentration (P > 0.05). HOMA-IR values in the 30 min-Ex, 45 min-Ex, and 60 min-Ex trials were lower than the Ctr (P < 0.03), but no significant differences were found in HOMA-IR among the exercise trials. The results suggest that for physically inactive individuals with metabolic syndrome, exercising at moderate intensity for 45 min effectively attenuates PHTG while exercise for 30 min is sufficient to improve insulin action.     

Does recombinant human Epo increase exercise capacity by means other than augmenting oxygen transport?

This study was performed to test the hypothesis that administration of recombinant human erythropoietin (rHuEpo) in humans increases maximal oxygen consumption by augmenting the maximal oxygen carrying capacity of blood. Systemic and leg oxygen delivery and oxygen uptake were studied during exercise in eight subjects before and after 13 wk of rHuEpo treatment and after isovolemic hemodilution to the same hemoglobin concentration observed before the start of rHuEpo administration. At peak exercise, leg oxygen delivery was increased from 1,777.0+/-102.0 ml/min before rHuEpo treatment to 2,079.8+/-120.7 ml/min after treatment. After hemodilution, oxygen delivery was decreased to the pretreatment value (1,710.3+/-138.1 ml/min). Fractional leg arterial oxygen extraction was unaffected at maximal exercise; hence, maximal leg oxygen uptake increased from 1,511.0+/-130.1 ml/min before treatment to 1,793.0+/-148.7 ml/min with rHuEpo and decreased after hemodilution to 1,428.0+/-111.6 ml/min. Pulmonary oxygen uptake at peak exercise increased from 3,950.0+/-160.7 before administration to 4,254.5+/-178.4 ml/min with rHuEpo and decreased to 4,059.0+/-161.1 ml/min with hemodilution (P=0.22, compared with values before rHuEpo treatment). Blood buffer capacity remained unaffected by rHuEpo treatment and hemodilution. The augmented hematocrit did not compromise peak cardiac output. In summary, in healthy humans, rHuEpo increases maximal oxygen consumption due to augmented systemic and muscular peak oxygen delivery.     

Attenuated hepatosplanchnic uptake of lactate during intense exercise in humans.

We evaluated whether the increase in blood lactate with intense exercise is influenced by a low hepatosplanchnic blood flow as assessed by indocyanine green dye elimination and blood sampling from an artery and the hepatic vein in eight men. The hepatosplanchnic blood flow decreased from a resting value of 1.6 +/- 0.1 to 0.7 +/- 0.1 (SE) l/min during exercise. Yet the hepatosplanchnic O2 uptake increased from 67 +/- 3 to 93 +/- 13 ml/min, and the output of glucose increased from 1.1 +/- 0.1 to 2.1 +/- 0.3 mmol/min (P < 0.05). Even at the lowest hepatosplanchnic venous hemoglobin O2 saturation during exercise of 6%, the average concentration of glucose in arterial blood was maintained close to the resting level (5.2 +/- 0.2 vs. 5.5 +/- 0.2 mmol/l), whereas the difference between arterial and hepatic venous blood glucose increased to a maximum of 22 mmol/l. In arterial blood, the concentration of lactate increased from 1.1 +/- 0.2 to 6.0 +/- 1.0 mmol/l, and the hepatosplanchnic uptake of lactate was elevated from 0.4 +/- 0.06 to 1.0 +/- 0.05 mmol/min during exercise (P < 0.05). However, when the hepatosplanchnic venous hemoglobin O2 saturation became low, the arterial and hepatosplanchnic venous blood lactate difference approached zero. Even with a marked reduction in its blood flow, exercise did not challenge the ability of the liver to maintain blood glucose homeostasis. However, it appeared that the contribution of the Cori cycle decreased, and the accumulation of lactate in blood became influenced by the reduced hepatosplanchnic blood flow.     

Glucose ingestion blunts hormone-sensitive lipase activity in contracting human skeletal muscle

To examine the effect of attenuated epinephrine and elevated insulin on intramuscular hormone sensitivity lipase activity (HSLa) during exercise, seven men performed 120 min of semirecumbent cycling (60% peak pulmonary oxygen uptake) on two occasions while ingesting either 250 ml of a 6.4% carbohydrate (GLU) or sweet placebo (CON) beverage at the onset of, and at 15 min intervals throughout, exercise. Muscle biopsies obtained before and immediately after exercise were analyzed for HSLa. Blood samples were simultaneously obtained from a brachial artery and a femoral vein before and during exercise, and leg blood flow was measured by thermodilution in the femoral vein. Net leg glycerol and lactate release and net leg glucose and free fatty acid (FFA) uptake were calculated from these measures. Insulin and epinephrine were also measured in arterial blood before and throughout exercise. During GLU, insulin was elevated (120 min: CON, 11.4 +/- 2.4, GLU, 35.3 +/- 6.9 pM, P < 0.05) and epinephrine suppressed (120 min: CON, 6.1 +/- 2.5, GLU, 2.1 +/- 0.9 nM; P < 0.05) compared with CON. Carbohydrate feeding also resulted in suppressed (P < 0.05) HSLa relative to CON (120 min: CON, 1.71 +/- 0.18, GLU, 1.27 +/- 0.16 mmol.min-1.kg dry mass-1). There were no differences in leg lactate or glycerol release when trials were compared, but leg FFA uptake was lower (120 min: CON, 0.29 +/- 0.06, GLU, 0.82 +/- 0.09 mmol/min) and leg glucose uptake higher (120 min: CON, 3.16 +/- 0.59, GLU, 1.37 +/- 0.37 mmol/min) in GLU compared with CON. These results demonstrate that circulating insulin and epinephrine play a role in HSLa in contracting skeletal muscle.     

Leg vasoconstriction during dynamic exercise with reduced cardiac output.

We evaluated whether a reduction in cardiac output during dynamic exercise results in vasoconstriction of active skeletal muscle vasculature. Nine subjects performed four 8-min bouts of cycling exercise at 71 +/- 12 to 145 +/- 13 W (40-84% maximal oxygen uptake). Exercise was repeated after cardioselective (beta 1) adrenergic blockade (0.2 mg/kg metoprolol iv). Leg blood flow and cardiac output were determined with bolus injections of indocyanine green. Femoral arterial and venous pressures were monitored for measurement of heart rate, mean arterial pressure, and calculation of systemic and leg vascular conductance. Leg norepinephrine spillover was used as an index of regional sympathetic activity. During control, the highest heart rate and cardiac output were 171 +/- 3 beats/min and 18.9 +/- 0.9 l/min, respectively. beta 1-Blockade reduced these values to 147 +/- 6 beats/min and 15.3 +/- 0.9 l/min, respectively (P < 0.001). Mean arterial pressure was lower than control during light exercise with beta 1-blockade but did not differ from control with greater exercise intensities. At the highest work rate in the control condition, leg blood flow and vascular conductance were 5.4 +/- 0.3 l/min and 5.2 +/- 0.3 cl.min-1.mmHg-1, respectively, and were reduced during beta 1-blockade to 4.8 +/- 0.4 l/min (P < 0.01) and 4.6 +/- 0.4 cl.min-1.mmHg-1 (P < 0.05). During the same exercise condition leg norepinephrine spillover increased from a control value of 2.64 +/- 1.16 to 5.62 +/- 2.13 nM/min with beta 1-blockade (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of high-intensity intermittent training on lactate and H+ release from human skeletal muscle

The study investigated the effect of training on lactate and H+ release from human skeletal muscle during one-legged knee-extensor exercise. Six subjects were tested after 7-8 wk of training (fifteen 1-min bouts at approximately 150% of thigh maximal O2 uptake per day). Blood samples, blood flow, and muscle biopsies were obtained during and after a 30-W exercise bout and an incremental test to exhaustion of both trained (T) and untrained (UT) legs. Blood flow was 16% higher in the T than in the UT leg. In the 30-W test, venous lactate and lactate release were lower in the T compared with the UT leg. In the incremental test, time to fatigue was 10.6 +/- 0.7 and 8.2 +/- 0.7 min, respectively, in the T and UT legs (P < 0.05). At exhaustion, venous blood lactate was 10.7 +/- 0.4 and 8.0 +/- 0.9 mmol/l in T and UT legs (P < 0.05), respectively, and lactate release was 19.4 +/- 3.6 and 10.6 +/- 2.0 mmol/min (P < 0.05). H+ release at exhaustion was higher in the T than in the UT leg. Muscle lactate content was 59.0 +/- 15.1 and 96.5 +/- 14.5 mmol/kg dry wt in the T and UT legs, and muscle pH was 6.82 +/- 0.05 and 6.69 +/- 0.04 in the T and UT legs (P = 0.06). The membrane contents of the monocarboxylate transporters MCT1 and MCT4 and the Na+/H+ exchanger were 115 +/- 5 (P < 0.05), 111 +/- 11, and 116 +/- 6% (P < 0.05), respectively, in the T compared with the UT leg. The reason for the training-induced increase in peak lactate and H+ release during exercise is a combination of an increased density of the lactate and H+ transporting systems, an improved blood flow and blood flow distribution, and an increased systemic lactate and H+ clearance.     

Fatty acid kinetics and carbohydrate metabolism during electrical exercise in spinal cord-injured humans

Motor center activity and reflexes from contracting muscle have been shown to be important for mobilization of free fatty acids (FFA) during exercise. We studied FFA metabolism in the absence of these mechanisms: during involuntary, electrically induced leg cycling in individuals with complete spinal cord injury (SCI). Healthy subjects performing voluntary cycling served as controls (C). Ten SCI (level of injury: C5-T7) and six C exercised for 30 min at comparable oxygen uptake rates (approximately 1 l/min), and [1-14C]palmitate was infused continuously to estimate FFA turnover. From femoral arteriovenous differences, blood flow, muscle biopsies, and indirect calorimetry, leg substrate balances as well as concentrations of intramuscular substrates were determined. Leg oxygen uptake was similar in the two groups during exercise. In SCI, but not in C, plasma FFA and FFA appearance rate fell during exercise, and plasma glycerol increased less than in C (P < 0.05). Fractional uptake of FFA across the working legs decreased from rest to exercise in all individuals (P < 0.05) but was always lower in SCI than in C (P < 0.05). From rest to exercise, leg FFA uptake increased less in SCI than in C subjects (14 +/- 3 to 57 +/- 20 vs. 41 +/- 13 to 170 +/- 57 micromol x min(-1) x leg(-1); P < 0.05). Muscle glycogen breakdown, leg glucose uptake, carbohydrate oxidation, and lactate release were higher (P < 0.05) in SCI than in C during exercise. Counterregulatory hormonal changes were more pronounced in SCI vs. C, whereas insulin decreased only in C. In conclusion, FFA mobilization, delivery, and fractional uptake are lower and muscle glycogen breakdown and glucose uptake are higher in SCI patients during electrically induced leg exercise compared with healthy subjects performing voluntary exercise. Apparently, blood-borne mechanisms are not sufficient to elicit a normal increase in fatty acid mobilization during exercise. Furthermore, in exercising muscle, FFA delivery enhances FFA uptake and inhibits carbohydrate metabolism, while carbohydrate metabolism inhibits FFA uptake.     

Neurohumoral responses during prolonged exercise in humans.

This study examined neurohumoral alterations during prolonged exercise with and without hyperthermia. The cerebral oxygen-to-carbohydrate uptake ratio (O2/CHO = arteriovenous oxygen difference divided by arteriovenous glucose difference plus one-half lactate), the cerebral balances of dopamine, and the metabolic precursor of serotonin, tryptophan, were evaluated in eight endurance-trained subjects during exercise randomized to be with or without hyperthermia. The core temperature stabilized at 37.9 +/- 0.1 degrees C (mean +/- SE) in the control trial, whereas it increased to 39.7 +/- 0.2 degrees C in the hyperthermic trial, with a concomitant increase in perceived exertion (P < 0.05). At rest, the brain had a small release of tryptophan (arteriovenous difference of -1.2 +/- 0.3 micromol/l), whereas a net balance was obtained during the two exercise trials. Both the arterial and jugular venous dopamine levels became elevated during the hyperthermic trial, but the net release from the brain was unchanged. During exercise, the O2/CHO was similar across trials, but, during recovery from the hyperthermic trial, the ratio decreased to 3.8 +/- 0.3 (P < 0.05), whereas it returned to the baseline level of approximately 6 within 5 min after the control trial. The lowering of O2/CHO was established by an increased arteriovenous glucose difference (1.1 +/- 0.1 mmol/l during recovery from hyperthermia vs. 0.7 +/- 0.1 mmol/l in control; P < 0.05). The present findings indicate that the brain has an increased need for carbohydrates during recovery from strenuous exercise, whereas enhanced perception of effort as observed during exercise with hyperthermia was not related to alterations in the cerebral balances of dopamine or tryptophan.     

Real-time assessment of postprandial fat storage in liver and skeletal muscle in health and type 2 diabetes

Liver and skeletal muscle triglyceride stores are elevated in type 2 diabetes and correlate with insulin resistance. As postprandial handling of dietary fat may be a critical determinant of tissue triglyceride levels, we quantified postprandial fat storage in normal and type 2 diabetes subjects. Healthy volunteers (n = 8) and diet-controlled type 2 diabetes subjects (n = 12) were studied using a novel 13C magnetic resonance spectroscopy protocol to measure the postprandial increment in liver and skeletal muscle triglyceride following ingestion of 13C-labeled fatty acids given with a standard mixed meal. The postprandial increment in hepatic triglyceride was rapid in both groups (peak increment controls: +7.3 +/- 1.5 mmol/l at 6 h, P = 0.002; peak increment diabetics: +10.8 +/- 3.4 mmol/l at 4 h, P = 0.009). The mean postprandial incremental AUC of hepatic 13C enrichment between the first and second meals (0 and 4 h) was significantly higher in the diabetes group (6.1 +/- 1.4 vs. 1.7 +/- 0.6 mmol x l(-1) x h(-1), P = 0.019). Postprandial increment in skeletal muscle triglyceride in the control group was small compared with the diabetic group, the mean 24-h postprandial incremental AUC being 0.2 +/- 0.3 vs. 1.7 +/- 0.4 mmol x l(-1) x h(-1) (P = 0.009). We conclude that the postprandial uptake of fatty acids by liver and skeletal muscle is increased in type 2 diabetes and may underlie the elevated tissue triglyceride stores and consequent insulin resistance.     

Glycogen loading alters muscle glycogen resynthesis after exercise.

This study compared muscle glycogen recovery after depletion of approximately 50 mmol/l (DeltaGly) from normal (Nor) resting levels (63.2 +/- 2.8 mmol/l) with recovery after depletion of approximately 50 mmol/l from a glycogen-loaded (GL) state (99.3 +/- 4.0 mmol/l) in 12 healthy, untrained subjects (5 men, 7 women). To glycogen load, a 7-day carbohydrate-loading protocol increased muscle glycogen 1.6 +/- 0.2-fold (P < or = 0.01). GL subjects then performed plantar flexion (single-leg toe raises) at 50 +/- 3% of maximum voluntary contraction (MVC) to yield DeltaGly = 48.0 +/- 1.3 mmol/l. The Nor trial, performed on a separate occasion, yielded DeltaGly = 47.5 +/- 4.5 mmol/l. Interleaved natural abundance (13)C-(31)P-NMR spectra were acquired and quantified before exercise and during 5 h of recovery immediately after exercise. During the initial 15 min after exercise, glycogen recovery in the GL trial was rapid (32.9 +/- 8.9 mmol. l(-1). h(-1)) compared with the Nor trial (15.9 +/- 6.9 mmol. l(-1). h(-1)). During the next 45 min, GL glycogen synthesis was not as rapid as in the Nor trial (0.9 +/- 2.5 mmol. l(-1). h(-1) for GL; 14.7 +/- 3.0 mmol. l(-1). h(-1) for Nor; P < or = 0.005) despite similar glucose 6-phosphate levels. During extended recovery (60-300 min), reduced GL recovery rates continued (1.3 +/- 0.5 mmol. l(-1). h(-1) for GL; 3.9 +/- 0.3 mmol. l(-1). h(-1) for Nor; P < or = 0.001). We conclude that glycogen recovery from heavy exercise is controlled primarily by the remaining postexercise glycogen concentration, with only a transient synthesis period when glycogen levels are not severely reduced.     

Estimations of muscle interstitial insulin, glucose, and lactate in type 2 diabetic subjects

Previous measurement of insulin in human muscle has shown that interstitial muscle insulin and glucose concentrations are approximately 30-50% lower than in plasma during hyperinsulinemia in normal subjects. The aims of this study were to measure interstitial muscle insulin and glucose in patients with type 2 diabetes to evaluate whether transcapillary transport is part of the peripheral insulin resistance. Ten patients with type 2 diabetes and ten healthy controls matched for sex, age, and body mass index were investigated. Plasma and interstitial insulin, glucose, and lactate (measured by intramuscular in situ-calibrated microdialysis) in the medial quadriceps femoris muscle were analyzed during a hyperinsulinemic euglycemic clamp. Blood flow in the contralateral calf was measured by vein plethysmography. At steady-state clamping, at 60-120 min, the interstitial insulin concentration was significantly lower than arterial insulin in both groups (409 +/- 86 vs. 1,071 +/- 99 pmol/l, P < 0.05, in controls and 584 +/- 165 vs. 1, 253 +/- 82 pmol/l, P < 0.05, in diabetic subjects, respectively). Interstitial insulin concentrations did not differ significantly between diabetic subjects and controls. Leg blood flow was significantly higher in controls (8.1 +/- 1.2 vs. 4.4 +/- 0.7 ml. 100 g(-1).min(-1) in diabetics, P < 0.05). Calculated glucose uptake was less in diabetic patients compared with controls (7.0 +/- 1.2 vs. 10.8 +/- 1.2 micromol. 100 g(-1).min(-1), P < 0.05, respectively). Arterial and interstitial lactate concentrations were both higher in the control group (1.7 +/- 0.1 vs. 1.2 +/- 0.1, P < 0. 01, and 1.8 +/- 0.1 vs. 1.2 +/- 0.2 mmol/l, P < 0.05, in controls and diabetics, respectively). We conclude that, during hyperinsulinemia, muscle interstitial insulin and glucose concentrations did not differ between patients with type 2 diabetes and healthy controls despite a significantly lower leg blood flow in diabetic subjects. It is suggested that decreased glucose uptake in type 2 diabetes is caused by insulin resistance at the cellular level rather than by a deficient access of insulin and glucose surrounding the muscle cell.     

Effect of carbohydrate ingestion on exercise metabolism

Five male cyclists were studied during 2 h of cycle ergometer exercise (70% VO2 max) on two occasions to examine the effect of carbohydrate ingestion on muscle glycogen utilization. In the experimental trial (CHO) subjects ingested 250 ml of a glucose polymer solution containing 30 g of carbohydrate at 0, 30, 60, and 90 min of exercise; in the control trial (CON) they received an equal volume of a sweet placebo. No differences between trials were seen in O2 uptake or heart rate during exercise. Venous blood glucose was similar before exercise in both trials, but, on average, was higher during exercise in CHO [5.2 +/- 0.2 (SE) mmol/l] compared with CON (4.8 +/- 0.1, P less than 0.05). Plasma insulin levels were similar in both trials. Muscle glycogen levels were also similar in CHO and CON both before and after exercise; accordingly, there was no difference between trials in the amount of glycogen used during the 2 h of exercise (CHO = 62.8 +/- 10.1 mmol/kg wet wt, CON = 56.9 +/- 10.1). The results of this study indicate that carbohydrate ingestion does not influence the utilization of muscle glycogen during prolonged strenuous exercise.     

Left ventricular function during arm exercise: influence of leg cycling and lower body positive pressure.

The purpose of this study was to characterize left ventricular (LV) diastolic filling and systolic performance during graded arm exercise and to examine the effects of lower body positive pressure (LBPP) or concomitant leg exercise as means to enhance LV preload in aerobically trained individuals. Subjects were eight men with a mean age (+/-SE) of 26.8 +/- 1.2 yr. Peak exercise testing was first performed for both legs [maximal oxygen uptake (Vo(2)) = 4.21 +/- 0.19 l/min] and arms (2.56 +/- 0.16 l/min). On a separate occasion, LV filling and ejection parameters were acquired using non-imaging scintography using in vivo red blood cell labeling with technetium 99(m) first during leg exercise performed in succession for 2 min at increasing grades to peak effort. Graded arm exercise (at 30, 60, 80, and 100% peak Vo(2)) was performed during three randomly assigned conditions: control (no intervention), with concurrent leg cycling (at a constant 15% leg maximal Vo(2)) or with 60 mmHg of LBPP using an Anti G suit. Peak leg exercise LV ejection fraction was higher than arm exercise (60.9 +/- 1.7% vs. 55.9 +/- 2.7%; P < 0.05) as was peak LV end-diastolic volume was reported as % of resting value (110.3 +/- 4.4% vs. 97 +/- 3.7%; P < 0.05) and peak filling rate (end-diastolic volume/s; 6.4 +/- 0.28% vs. 5.2 +/- 0.25%). Concomitant use of either low-intensity leg exercise or LBPP during arm exercise failed to significantly increase LV filling or ejection parameters. These observations suggest that perturbations in preload fail to overcome the inherent hemodynamic conditions present during arm exercise that attenuate LV performance.     

Cerebral metabolic response to submaximal exercise.

We studied cerebral oxygenation and metabolism during submaximal cycling in 12 subjects. At two work rates, middle cerebral artery blood velocity increased from 62 +/- 3 to 63 +/- 3 and 70 +/- 5 cm/s as did cerebral oxygenation determined by near-infrared spectroscopy. Oxyhemoglobin increased by 10 +/- 3 and 25 +/- 3 micromol/l (P < 0. 01), and there was no significant change in brain norepinephrine spillover. The arterial-to-internal-jugular-venous (a-v) difference for O(2) decreased at low-intensity exercise (from 3.1 +/- 0.1 to 2. 9 +/- 0.1 mmol/l; P < 0.05) and recovered at moderate exercise (to 3. 3 +/- 0.1 mmol/l). The profile for glucose was similar: its a-v difference tended to decrease at low-intensity exercise (from 0.55 +/- 0.05 to 0.50 +/- 0.02 mmol/l) and increased during moderate exercise (to 0.64 +/- 0.04 mmol/l; P < 0.05). Thus the molar ratio (a-v difference, O(2) to glucose) did not change significantly. However, when the a-v difference for lactate (0.02 +/- 0.03 to 0.18 +/- 0.04 mmol/l) was taken into account, the O(2)-to-carbohydrate ratio decreased (from 6.1 +/- 0.4 to 4.7 +/- 0.3; P < 0.05). The enhanced cerebral oxygenation suggests that, during exercise, cerebral blood flow increases in excess of the O(2) demand. Yet it seems that during exercise not all carbohydrate taken up by the brain is oxidized, as brain lactate metabolism appears to lower the balance of O(2)-to-carbohydrate uptake.     

Influence of active muscle mass on glucose homeostasis during exercise in humans

To study the effect of increasing amounts of exercising muscle mass on the relationship between glucose mobilization and peripheral glucose uptake, seven young men (23-28 yr) bicycled for 70 min at a work load of 55-60% VO2max. From minute 30 to 50, arm cranking was added and total work load increased to 82 +/- 4% VO2max. During leg exercise, hepatic glucose production (Ra) increased in parallel with peripheral glucose uptake (Rd) and euglycemia was maintained. During arm + leg exercise, Ra increased more than Rd and accordingly plasma glucose increased from 5.11 +/- 0.22 to 8.00 +/- 0.66 mmol/l (P less than 0.05). Plasma catecholamines increased three- to four-fold more during arm + leg exercise than during leg exercise. Leg glucose uptake increased with time regardless of arm cranking. Net leg lactate release during leg exercise was reverted to a net leg lactate uptake during arm + leg exercise. The rate of glycogen breakdown in exercising leg muscle was not altered by addition of arm cranking. In conclusion, when large amounts of muscle mass are active, plasma catecholamines increase sharply and mobilization of glucose exceeds peripheral glucose uptake. This indicates that mechanisms other than feedback regulation to maintain euglycemia are involved in hormonal and substrate mobilization during intense exercise in humans.