Role of beta-adrenergic mechanisms during exercise in poorly controlled diabetes

To examine the beta-adrenergic effects of the catecholamines in poorly controlled diabetes, we have studied insulin-deprived alloxan-diabetic (A-D) dogs during 90 min of moderate exercise (100 m/min, 10-12 degrees) alone (C) or with propranolol (5 micrograms . kg-1 . min-1) (P) or combined P and somatostatin infusion (0.5 microgram . kg-1 . min-1) (P + St). In P, in contrast to C, immunoreactive glucagon (IRG) rose only after 50 min of exercise. However, hepatic glucose production (Ra) rose normally. In P + St, IRG fell 50% below basal, and the Ra response to exercise was abolished. Interestingly, in P and P + St, glucose metabolic clearance rate (MCR) rose by 400% above the inadequate MCR response to exercise in C, despite 30% lower insulin levels. Compared with C, free fatty acids (FFA) and lactate were sharply reduced during P and P + St. Plasma glucose (G) did not change in C, but due to elevated glucose uptake, G fell over 120 mg/dl in P, and due to diminished Ra, G fell 170 mg/dl in P + St. Norepinephrine was similar in all groups. Epinephrine and cortisol were higher in P + St by 90 min of exercise, perhaps as a result of hypoglycemia. In summary, during exercise in poorly controlled A-D dogs, beta-blockade does not appear to affect Ra; beta-blockade leads to diminished mobilization of extrahepatic substrate as evidenced by reduced FFA and lactate levels; beta-blockade increases MCR to levels seen in normal dogs during exercise alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

GLUCOSE KINETICS IN NEONATAL ELEPHANT SEALS DURING POSTWEANING APHAGIA

Northern elephant seal ( Mirounga angustirostris )pups undergo extended periods of terrestrial aphagia after weaning and exhibit a paradoxical fasting hyperglycemia. To investigate the details of glucose metabolism during this period, reversible and irreversible radiotracers were used to determine the body mass of glucose, and rates of glucose turnover, recycling, and oxidation in fasting seal pups. A typical 75 kg pup has a glucose mass of about 4.5 g (60 mg/kg), and a blood glucose concentration of about 174 mg/dl. Blood glucose removal rate was about 30 grams per day (17 mg/kg · h^-1), but less than 2.5% of this glucose was oxidized, contributing less than 1% of the total metabolic rate. About 20% of the glucose pool was removed from the blood per hour, yielding a turnover time in the vascular space of about five hours. Most glucose removed from the blood was returned to the blood by recycling. Such recycling may contribute to mechanisms which prolong survival during fasting, such as high rates of triacyclglycerol turnover, synthesis of new protein pools, low ketone levels, and the Cori cycle which is important during diving.     

Glucoregulatory and hormonal responses to repeated bouts of intense exercise in normal male subjects.

Glucose turnover and its regulation were studied during and after two identical bouts of intense exhaustive exercise separated by 1 h to define differences in response. Six lean young postabsorptive male subjects exercised at approximately 100% maximal O2 uptake (3.7 +/- 0.3 l/min) for 13.0 +/- 0.7 min for the first (EX1) and 13.2 +/- 0.8 min for the second (EX2) bout. Plasma glucose increased during EX1 and peaked at 7.0 +/- 0.6 mmol/l in early recovery but to 5.8 +/- 0.5 mmol/l (P less than 0.05) after EX2, and both the hyperglycemic and the hyperinsulinemic responses were less after EX2 (P less than 0.015, analysis of variance). The hyperglycemia was due to lesser increments in glucose utilization (Rd) (3-fold resting) than glucose production (Ra) (7-fold) toward exhaustion and for 7 min of recovery. The rise in Rd was more rapid (P less than 0.05) and metabolic clearance rate was greater during (P = 0.015) and from 9 to 60 min after EX2, and Ra also remained higher during recovery (P less than 0.05). Marked and similar increments in plasma norepinephrine (18-fold) and epinephrine (14-fold) occurred with both bouts. Plasma glucagon increments were small and not different. Therefore, 1) more circulating glucose was used with EX2, 2) greater metabolic clearance rate during and after EX2 suggests local muscle adaptations due to EX1, and 3) significant correlations (P less than 0.002) between plasma norepinephrine and Ra (r = 0.82) and Ra - Rd (r = 0.52) and between epinephrine and Ra (r = 0.71) and Ra - Rd (r = 0.48) suggest a major regulatory role for the catecholamine responses.     

Effects of training on glucose metabolism of gluconeogenesis-inhibited short-term-fasted rats

To evaluate the effects of endurance training on gluconeogenesis and blood glucose homeostasis, trained as well as untrained short-term-fasted rats were injected with mercaptopicolinic acid (MPA), a gluconeogenic inhibitor, or the injection vehicle. Glucose kinetics were assessed by primed-continuous venous infusion of [U-14C]- and [6-3H]glucose at rest and during submaximal exercise at 13.4 m/min on level grade. Arterial blood was sampled for the determination of blood glucose and lactate concentrations and specific activities. In resting untrained sham-injected rats, blood glucose and lactate were 7.6 +/- 0.2 and 1.3 +/- 0.1 mM, respectively; glucose rate of appearance (Ra) was 71.1 +/- 12.1 mumol.kg-1.min-1. MPA treatment lowered blood glucose, raised lactate, and decreased glucose Ra. Trained animals had significantly higher glucose Ra at rest and during exercise. At rest, trained MPA-treated rats had lower blood glucose, higher blood lactate, and similar glucose Ra and disappearance rates (Rd) than trained sham-injected animals. Exercising sham-injected untrained animals had increased blood glucose and glucose Ra compared with rest. Exercising trained sham-injected rats had increased blood glucose and glucose Ra and Rd but no change in blood lactate compared with untrained sham-injected animals. In the trained animals during exercise, MPA treatment increased blood lactate and decreased blood glucose and glucose Ra and Rd. There was no measurable glucose recycling in trained or untrained MPA-treated animals either at rest or during submaximal exercise. There was no difference in running time to exhaustion between trained and untrained MPA-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Acute exposure to GH during exercise stimulates the turnover of free fatty acids in GH-deficient men.

The secretion of growth hormone (GH) increases acutely during exercise, but whether this is associated with the concomitant alterations in substrate metabolism has not previously been studied. We examined the effects of acute GH administration on palmitate, glucose, and protein metabolism before, during, and after 45 min of moderate-intensity aerobic exercise in eight GH-deficient men (mean age = 40.8 +/- 2.9 yr) on two occasions, with (+GH; 0.4 IU GH) and without GH administered (-GH). A group of healthy controls (n = 8, mean age = 40.4 +/- 4.2 yr) were studied without GH. The GH replacement during exercise on the +GH study mimicked the endogenous GH profile seen in healthy controls. No significant difference in resting free fatty acid (FFA) flux was found between study days, but during exercise a greater FFA flux was found when GH was administered (211 +/- 26 vs. 168 +/- 28 micromol/min, P < 0.05) and remained elevated throughout recovery (P < 0.05). With GH administered, the exercise FFA flux was not significantly different from that observed in control subjects (188 +/- 14 micromol/min), but the recovery flux was greater on the +GH day than in the controls (169 +/- 17 vs. 119 +/- 11 micromol/min, respectively, P < 0.01). A significant time effect (P < 0.01) for glucose rate of appearance from rest to exercise and recovery occurred in the GH-deficient adults and the controls, whereas there were no differences in glucose rate of disappearance. No significant effect across time was found for protein muscle balance. In conclusion, 1) acute exposure to GH during exercise stimulates the FFA release and turnover in GH-deficient adults, 2) GH does not significantly impact glucose or protein metabolism during exercise, and 3) the exercise-induced secretion of GH plays a significant role in the regulation of fatty acid metabolism.     

Interrelationship of FFA and glycerol turnovers in resting and exercising dogs.

Dogs with indwelling arterial and venous catheters ran on a treadmill on a 10% or on a 15% slope at 100 m/min. Glycerol turnover ([2-3H]-glycerol) and FFA turnover ([1-14C]palmitate) were measured simultaneously. Both turnovers were greatly increased by exercise. Similar increases were produced in resting dogs by norepinephrine infusions (0.5 mug/kg-min). At rest, as well as during exercise, there was a straight-line correlation between the ratio of disappearance of each substrate and their respective plasma concentrations. Over a wide range there was a straight-line correlation between the rate of production of FFA (RaFFA) and that of glycerol (RaGLY) at rest as well as during exercise. At any given RaFFA, RaGLY was higher in the running than in the resting dog. At rest the ratio of RaFFA/RaGLY was found to give the theoretical value of 3.0 only when RaFFA was 10-15 mumol/kg-min, below this the ratio was lower and above this it was higher. During exercise the ratio was lower than at rest and at heavier load lower than at lighter work. The results suggest that in vivo a combination of partial and complete lipolysis as well as reesterification occurs. The glucose equivalent of the glycerol turnover (if 100% converted) represents (under the given experimental conditions) 14-18% of the hepatic glucose output on the 15% slope and 20-25% of it on the 10% slope.     

Fuel homeostasis in the harbor seal during submerged swimming

1. The turnover rates and oxidation rates of plasma glucose, lactate, and free fatty acids (FFA) were measured in three harbor seals (average mass = 40 kg) at rest or during voluntary submerged swimming in a water flume at 35% (1.3 m.s-1) and 50% (2 m.s-1) of maximum oxygen consumption (MO2max). 2. For seals resting in water, the total turnover rates for glucose, lactate, and FFA were 23.2, 26.2, and 7.5 mumols.min-1.kg-1, respectively. Direct oxidation of these metabolites accounted for approximately 7%, 27%, and 33% of their turnover and 3%, 7%, and 18% of the total ATP production, respectively. 3. For swimming seals, MO2max was achieved at a drag load equivalent to a speed of 3 m.s-1 and averaged 1.85 mmol O2.min-1.kg-1, which is 9-fold greater than resting metabolism in water at 18 degrees C. 4. At 35% and 50% MO2max, glucose turnover and oxidation rates did not change from resting levels. Glucose oxidation contributed about 1% of the total ATP production during swimming. 5. At 50% MO2max, lactate turnover and anaerobic ATP production doubled, but the steady state plasma lactate concentration remained low at 1.1 mM. Lactate oxidation increased 63% but still contributed only 4% of the total ATP production. Anaerobic metabolism contributed about 1% of the total ATP production at rest and during swimming. 6. The plasma FFA concentration and turnover rate increased only 24% and 37% over resting levels, respectively, at 50% MO2max. However, the oxidation rate increased almost 3.5-fold and accounted for 85% of the turnover.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of prior exercise and caffeine ingestion on metabolic rate and hormones in young adult males

The purposes of this study were to examine (a) the effects of acute exercise on metabolic rate 24 and 48 h postexercise and (b) the interaction of acute exercise and the thermic effect of caffeine on metabolic rate and hormonal changes during the late postexercise recovery period. In six young males, who were regular consumers of caffeine, resting energy expenditure was measured before and after caffeine (5 mg.kg-1) and placebo ingestion under the following conditions: (i) control (e.g., no prior exercise), (ii) 24 h postexercise, and (iii) 48 h postexercise. Blood samples were drawn for plasma glucose, insulin, glycerol, free fatty acids, catecholamines, and thyroid hormones (triiodothyronine, thyroxine, and free thyroxine). Results showed that acute exercise did not exert a detectable effect on resting metabolic rate in the late postexercise recovery period, that is, resting metabolic rate was similar among the conditions of control (1.17 +/- 0.12 kcal.min-1), 24 h postexercise (1.16 +/- 0.12), and 48 h postexercise (1.16 +/- 0.11). Caffeine ingestion increased metabolic rate (approximately 7%), but the thermic effect was not different among the experimental conditions. Plasma insulin and norepinephrine were lower after caffeine ingestion, whereas an increase in plasma free fatty acids was noted. Other hormones and substrates did not change significantly in response to caffeine ingestion. Furthermore, the hormonal and substrate milieu was not significantly different 24 and 48 h postexercise when compared with the control condition. Our results support the view that acute exercise does not alter the resting metabolic rate in the late postexercise recovery period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Substrate metabolism during different exercise intensities in endurance-trained women.

We have studied eight endurance-trained women at rest and during exercise at 25, 65, and 85% of maximal oxygen uptake. The rate of appearance (R(a)) of free fatty acids (FFA) was determined by infusion of [(2)H(2)]palmitate, and fat oxidation rates were determined by indirect calorimetry. Glucose kinetics were assessed with [6,6-(2)H(2)]glucose. Glucose R(a) increased in relation to exercise intensity. In contrast, whereas FFA R(a) was significantly increased to the same extent in low- and moderate-intensity exercise, during high-intensity exercise, FFA R(a) was reduced compared with the other exercise values. Carbohydrate oxidation increased progressively with exercise intensity, whereas the highest rate of fat oxidation was during exercise at 65% of maximal oxygen uptake. After correction for differences in lean body mass, there were no differences between these results and previously reported data in endurance-trained men studied under the same conditions, except for slight differences in glucose metabolism during low-intensity exercise (Romijn JA, Coyle EF, Sidossis LS, Gastaldelli A, Horowitz JF, Endert E, and Wolfe RR. Am J Physiol Endocrinol Metab 265: E380-E391, 1993). We conclude that the patterns of changes in substrate kinetics during moderate- and high-intensity exercise are similar in trained men and women.     

Leg and arm lactate and substrate kinetics during exercise

To study the role of muscle mass and muscle activity on lactate and energy kinetics during exercise, whole body and limb lactate, glucose, and fatty acid fluxes were determined in six elite cross-country skiers during roller-skiing for 40 min with the diagonal stride (Continuous Arm + Leg) followed by 10 min of double poling and diagonal stride at 72-76% maximal O(2) uptake. A high lactate appearance rate (R(a), 184 +/- 17 micromol x kg(-1) x min(-1)) but a low arterial lactate concentration ( approximately 2.5 mmol/l) were observed during Continuous Arm + Leg despite a substantial net lactate release by the arm of approximately 2.1 mmol/min, which was balanced by a similar net lactate uptake by the leg. Whole body and limb lactate oxidation during Continuous Arm + Leg was approximately 45% at rest and approximately 95% of disappearance rate and limb lactate uptake, respectively. Limb lactate kinetics changed multiple times when exercise mode was changed. Whole body glucose and glycerol turnover was unchanged during the different skiing modes; however, limb net glucose uptake changed severalfold. In conclusion, the arterial lactate concentration can be maintained at a relatively low level despite high lactate R(a) during exercise with a large muscle mass because of the large capacity of active skeletal muscle to take up lactate, which is tightly correlated with lactate delivery. The limb lactate uptake during exercise is oxidized at rates far above resting oxygen consumption, implying that lactate uptake and subsequent oxidation are also dependent on an elevated metabolic rate. The relative contribution of whole body and limb lactate oxidation is between 20 and 30% of total carbohydrate oxidation at rest and during exercise under the various conditions. Skeletal muscle can change its limb net glucose uptake severalfold within minutes, causing a redistribution of the available glucose because whole body glucose turnover was unchanged.     

Turnover of free fatty acids during recovery from exercise.

The turnover of plasma free fatty acid (FFA) was studied during the recovery from exercise with the aid of a continuous infusion of 14C-labeled oleic acid. Arterial FFA reached a maximum of twice the exercise value after 6 min of recovery and was still 75% above the basal level after 20 min. Within 2 min after exercise, plasma radioactivity had increased and the specific activity of plasma oleic acid had fallen. The rate of uptake of FFA from the plasma pool rsoe by 40% during the first minutes after exercise. The rate of release of FFA to the plasma pool showed a peak 2 min after exercise and was thereafter about 40 mumol/min lower than the rate of uptake. The fractional turnover of FFA decreased to resting levels within 5-10 min after exercise. It is concluded that the postexercise peak in arterial FFA is a consequence of augmented release of FFA into the plasma pool above the level during exercise, possibly related to the release of sympathetic vasoconstrictor tone. As a consequence, the rate of removal of FFA rises at the end of exercise and remains augmented above the basal level for as long as the arterial concentration is increased.     

Balancing conflicting metabolic demands of exercise and diving

During enforced diving, aquatic animals activate a set of physiological reflexes (apnea, bradycardia, peripheral vasoconstriction), which are termed the diving response and are in effect the first line of defense against hypoxia. At least in the Weddell seal, this strategy is now known also to be used in voluntary diving at sea, but the response is necessarily modified to accommodate potentially conflicting demands of diving and swimming exercise. The main modification appears to involve skeletal muscles used in swimming, which, because of their high energy requirements, must be powered by aerobic metabolism. Thus they must remain perfused at rates porportional to swimming velocity (which is why heart rates are adjusted to swimming velocity). The required regulation of O2 delivery is achieved at least in part by a well-paced release of oxygenated red blood cells, stored at the beginning of the dive apparently in the spleen. The main metabolic difference between laboratory and voluntary diving is that, in the latter, working muscles serve as a sink for lactate and thus the entry rates of lactate into the plasma can be balanced by exit rates from the plasma; the maintenance of this balance means that no excess lactate remains for a lactate washout in postdiving exercise except under long, exploratory diving. Even in the latter long dives, however, the amount of lactate formed is far less than would be expected if the energetic shortfall caused by hypoperfusion and O2 lack were made up by anaerobic glycolysis (Pasteur effect). Consequently, during diving, hypoperfused tissues necessarily sustain a metabolic arrest of variable degrees as a mechanism of defense against hypoxia.     

Menstrual cycle phase and sex influence muscle glycogen utilization and glucose turnover during moderate-intensity endurance exercise

Numerous studies from our and other laboratories have shown that women have a lower respiratory exchange ratio (RER) during exercise than equally trained men, indicating a greater reliance on fat oxidation. Differences in estrogen concentration between men and women likely play a role in this sex difference. Differing estrogen and progesterone concentrations during the follicular (FP) and luteal (LP) phases of the female menstrual cycle suggest that fuel use may also vary between phases. The purpose of the current study was to determine the effect of menstrual cycle phase and sex upon glucose turnover and muscle glycogen utilization during endurance exercise. Healthy, recreationally active young women (n = 13) and men (n = 11) underwent a primed constant infusion of [6,6-2H]glucose with muscle biopsies taken before and after a 90-min cycling bout at 65% peak O2 consumption. LP women had lower glucose rate of appearance (Ra, P = 0.03), rate of disappearance (Rd, P = 0.03), and metabolic clearance rate (MCR, P = 0.04) at 90 min of exercise and lower proglycogen (P = 0.04), macroglycogen (P = 0.04), and total glycogen (P = 0.02) utilization during exercise compared with FP women. Men had a higher RER (P = 0.02), glucose Ra (P = 0.03), Rd (P = 0.03), and MCR (P = 0.01) during exercise compared with FP women, and men had a higher RER at 75 and 90 min of exercise (P = 0.04), glucose Ra (P = 0.01), Rd (P = 0.01), and MCR (P = 0.001) and a greater PG utilization (P = 0.05) compared with LP women. We conclude that sex, and to a lesser extent menstrual cycle, influence glucose turnover and glycogen utilization during moderate-intensity endurance exercise.     

Role of the glucose cycle in control of net glucose flux in exercising humans

The hepatic glucose cycle involves the production of plasma glucose from glucose 6-phosphate and the simultaneous conversion of glucose back to glucose 6-phosphate. We have evaluated the role of the glucose cycle in the regulation of plasma glucose concentration during exercise at 70% of maximal O2 uptake and during recovery in five normal volunteers. Total glucose flux was measured by use of [2-2H]glucose (Ra2), net glucose flux through the glucose cycle was determined with [6,6-2H2]glucose (Ra6), and the rate of glucose cycling was determined by Ra2 - Ra6. Gas chromatography-mass spectrometry was used for analysis of isotopic enrichment. At rest, 33% of total glucose flux was recycled. In exercise, total flux increased 300%, but so did glucose cycling, which means that there was no change in the percentage of flux recycled. In recovery, both total flux and the rate of recycling returned rapidly to the resting value. We therefore conclude that whereas total glucose production can respond extremely quickly to large changes in energy requirements caused by exercise, thereby enabling maintenance of a constant blood glucose concentration, glucose cycling does not have an important role in amplifying the control of net hepatic glucose flux through the glucose cycle.     

Combined effects of cold and somatostatin on glucose kinetics in dogs

The role of the endocrine pancreas in glucose production (Ra), utilization (Rd), and metabolic clearance (R'd) was investigated during acute exposure to cold in normal normothermic dogs. Two ambient temperatures (TaN = +25 degrees C and TaC = -21 degrees C) were selected. At TaC, metabolic rate and glucose turnover of the shivering dogs were 4.3 and 2.4 times, respectively, higher than in dogs resting at TaN. As compared with the pre-experimental period, somatostatin infusion at TaN induced a 25% (arterial) and 34% (portal) glucagon deficiency, while insulin concentration dropped by 59% (arterial) and 74% (portal). Similar values were obtained at TaC for glucagon (39% arterial and 47% portal) and for insulin (52% arterial and 56% portal). At TaN, these simultaneous hormonal alterations provoked a slight reduction in plasma glucose concentration which levelled down to 4.4 mM. This reduction was due to a decrease in Ra, followed by a parallel decrease in Rd whereas R'd remained unchanged. At TaC, plasma glucose concentration dropped to the same level but quickly rose again during somatostatin infusion. This rise was due to a larger reduction in Rd than in Ra, accompanied by an abrupt fall in R'd. This reduction in R'd appears to be an important mechanism able to restore euglycemia during global pancreatic hormone deficiency in cold exposed dogs.     

Effect of liver glycogen content on glucose production in running rats

The influence of supranormal compared with normal hepatic glycogen levels on hepatic glucose production (Ra) during exercise was investigated in chronically catheterized rats. Supranormal hepatic glycogen levels were obtained by a 24-h fast-24-h refeeding regimen. During treadmill running for 35 min at a speed of 21 m/min, Ra and plasma glucose increased more (P less than 0.05) and liver glucogen breakdown was larger in fasted-refed compared with control rats, although the stimuli for Ra were higher in control rats, the plasma concentrations of insulin and glucose being lower (P less than 0.05) in control compared with fasted-refed rats. Also, plasma concentrations of glucagon and both catecholamines tended to be higher and muscle glycogenolysis lower in control compared with fasted-refed rats. Lipid metabolism was similar in the two groups. The results indicate that hepatic glycogenolysis during exercise is directly related to hepatic glycogen content. The smaller endocrine glycogenolytic signal in face of higher plasma glucose concentrations in fasted-refed compared with control rats is indicative of metabolic feedback control of glucose mobilization during exercise. However, the higher exercise-induced increase in Ra, plasma glucose, and liver glycogen breakdown in fasted-refed compared with control rats indicates that metabolic feedback mechanisms are not able to accurately match Ra to the metabolic needs of working muscles.     

Effect of hematocrit reduction on hormonal and metabolic responses to exercise

We wished to determine the effect of a 25% hematocrit reduction on glucoregulatory hormone release and glucose fluxes during exercise. In five anemic dogs, plasma glucose fell by 21 mg/dl and in five controls by 7 mg/dl by the end of the 90-min exercise period. After 50 min of exercise, hepatic glucose production (Ra) and glucose metabolic clearance rate (MCR) began to rise disproportionately in anemics compared with controls. By the end of exercise, the increase in Ra was almost threefold higher (delta 15.1 +/- 3.4 vs. delta 5.2 +/- 1.3 mg X kg-1 X min-1) and MCR nearly fourfold (delta 24.6 +/- 8.8 vs. delta 6.5 +/- 1.3 ml X kg-1 X min-1). Exercise with anemia, in relation to controls resulted in elevated levels of glucagon [immunoreactive glucagon (IRG) delta 1,283 +/- 507 vs delta 514 +/- 99 pg/ml], norepinephrine (delta 1,592 +/- 280 vs. delta 590 +/- 155 pg/ml), epinephrine (delta 2,293 +/- 994 vs. delta 385 +/- 186 pg/ml), cortisol (delta 6.7 +/- 2.2 vs. delta 2.1 +/- 1.0 micrograms/dl) and lactate (delta 12.1 +/- 2.2 vs. delta 4.2 +/- 1.8 mg/dl) after 90 min. Immunoreactive insulin and free fatty acids were similar in both groups. In conclusion, exercise with a 25% hematocrit reduction results in 1) elevated lactate, norepinephrine, epinephrine, cortisol, and IRG levels, 2) an increased Ra which is likely related to the increased counterregulatory response, and 3) we speculate that a near fourfold increase in MCR is related to metabolic changes due to hypoxia in working muscle.(ABSTRACT TRUNCATED AT 250 WORDS)     

DEVELOPMENT OF A BIMODAL HEART RATE PATTERN IN UNDISTURBED FETAL HARBOR SEALS

Fetal and maternal heart rates were studied in unrestrained, pregnant harbor seals during the last third of gestation. Heart rates were recorded while the mothers were resting on land or performing trained simulated dives of up to 2.25 min. Data from resting mothers showed the development of a bimodal or two-speed fetal heart rate pattern during late gestation. The mean faster and slower fetal heart rates at term were 125 ± 3.7 and 79 ± 3.1 (mean + SEM) respectively. The amount of fetal bradycardia observed increased steadily towards term, and fetal heart rate changes were not correlated with changes in maternal heart rate or maternal respiration. The bimodal fetal heart rate was also seen during the simulated dives, and no decrease in either the faster or slower heart rate was found. Heart rates from resting, unrestrained harbor seal pups were also studied. The pups displayed a bimodal heart rate similar to the fetuses' with the slower rate occurring during breath-holds. The bradycardia in the pups was equivalent to the slower fetal heart rate. These findings suggest that the regulatory mechanism that determines the apneic bradycardia in young harbor seals during non-stressful conditions develops in the last quarter of gestation.     

Effect of glucose on plasma glucagon and free fatty acids during prolonged exercise

The effects of glucose ingestion on the changes in blood glucose, FFA, insulin and glucagon levels induced by a prolonged exercise at about 50% of maximal oxygen uptake were investigated. Healthy volunteers were submitted to the following procedures: 1. a control test at rest consisting of the ingestion of 100 g glucose, 2. an exercise test without, or 3. with ingestion of 100 g of glucose. Exercise without glucose induced a progressive decrease in blood glucose and plasma insulin; plasma glucagon rose significantly from the 60th min onward (+45 pg/ml), the maximal increase being recorded during the 4th h of exercise (+135 pg/ml); plasma FFA rose significantly from the 60th min onward and reached their maximal values during the 4th h of exercise (2177 +/- 144 muEq/l, m +/- SE). Exercise with glucose ingestion blunted almost completely the normal insulin response to glucose. Under these conditions, exercise did not increase plasma glucagon before the 210th min; similarly, the exercise-induced increase in plasma FFA was markedly delayed and reduced by about 60%. It is suggested that glucose availability reduces exercise-induced glucagon secretion and, possibly consequently, FFA mobilization.