Skeletal muscle substrate utilization is altered by acute and acclimatory temperature in the American bullfrog (Lithobates catesbeiana).

We investigated the effect of acute and acclimatory temperature on the relative contribution of g9lucose and lactate to metabolism in resting sartorius muscle of the American bullfrog (Lithobates catesbeiana). We examined the fate of these metabolites in vitro by supplying radiolabeled [(14)C]glucose, [(14)C]lactate and [(14)C]palmitate to isolated muscle bundles from frogs (1) acutely exposed to incubation conditions of 5, 15 or 25 degrees C, (2) acclimated for 2-6 weeks to 5 or 25 degrees C or (3) acclimated for 2-6 weeks to 5 or 25 degrees C and the muscles incubated at 15 degrees C. Under all three temperature conditions tested, net rate of lactate metabolism exceeded that of glucose. Acute exposure to 5 degrees C reduced net rate of glucose metabolism by 15x and net lactate metabolism by 10x as compared with 25 degrees C-exposed tissues. Acclimation to 5 degrees C favored glucose storage as glycogen and increased the proportion of lactate oxidized (versus stored or converted to glucose) when compared with 25 degrees C-acclimated tissues. Net rates of storage of lactate as glycogen (glyconeogenesis) were significantly higher in muscles from 5 degrees C-acclimated frogs during incubation at a common temperature of 15 degrees C. These data suggest that lactate is the predominant fuel for resting skeletal muscle over this temperature range, and particularly so under cold conditions. Ready use of lactate as a substrate, and enhancement of glyconeogenic pathways in response to cold acclimation, could play a role in the tolerance of this species to seasonal temperature changes by promoting sequestration and storage of available substrate under cold conditions.

Scaling the duration of activity relative to body mass results in similar locomotor performance and metabolic costs in lizards.

This study examines the physiological response to locomotion in lizards following bouts of activity scaled to body mass. We evaluate this method as a way to compare locomotor energetics among animals of varying body mass. Because most of the costs of brief activity in reptiles are repaid during recovery we focus on the magnitude and duration of the excess post-exercise oxygen consumption (EPOC). Lizards ranging from 3 g to 2400 g were run on a treadmill for durations determined by scaling the run time of each animal to the 1/4 power of body mass and allowing each animal to run at its maximum speed for that duration. This protocol resulted in each species traveling the same number of body lengths and incurring similar factorial increases in V(O(2)). Following activity, EPOC volume (ml O(2)) and the cost of activity per body length traveled (ml O(2) per body length) scaled linearly with body mass. This study shows that the mass-specific costs of activity over an equivalent number of body lengths are similar across a broad range of body mass and does not show the typical patterns of allometric scaling seen when cost of locomotion are expressed on a per meter basis. Under field conditions larger animals are likely to travel greater absolute distances in a given bout of activity than smaller animals but may travel a similar number of body lengths. This study suggests that if locomotor costs are measured on a relative scale (ml O(2) per body length traveled), which reflects these differences in daily movement distances, that locomotor efficiency is similar across a wide range of body mass.

Characterization of circannual patterns of metabolic recovery from activity in Rana catesbeiana at 15 degrees C.

We characterized carbohydrate metabolism following activity in the American bullfrog, Rana catesbeiana, and compared whole body metabolic profiles between two seasons. Forty-eight adult male Rana catesbeiana were chronically cannulated and injected with [U-(14)C]L-lactic acid sodium salt in either summer (June) or winter (January) after acclimation for 2 weeks at 15 degrees C with a 12 h:12 h L:D photoperiod. Following injection with [(14)C]lactate, frogs were either allowed to rest for 240 min (REST), hopped for 2 min on a treadmill and immediately sacrificed (PE), or hopped for 2 min on a treadmill and allowed to recover for 240 min (REC 4). Exercise caused a significant increase in blood lactate level from 2.7+/-0.1 mmol l(-1) at rest to 17.0+/-2.1 mmol l(-1) immediately following exercise. This increase persisted throughout the recovery period, with average blood lactate level only reduced to 13.7+/-1.1 mmol l(-1) after 240 min of recovery, despite complete recovery of intramuscular lactate levels. Lactate levels were not significantly different between seasons in any treatment (REST, PE, REC4), in either gastrocnemius muscle or blood. The vast majority of [(14)C]lactate was recovered in the muscle, in both winter (86.3%) and summer (87.5%). Season had no effect on total amount of (14)C label recovered. [(14)C]Lactate was measured in the forms of lactate, glucose and glycogen, in the liver and the muscle sampled. The most robust difference found in seasonal metabolism was that both the liver and the gastrocnemius contained significantly higher levels of intracellular free glucose under all treatments in winter. These data suggest that, overall, bullfrogs accumulate and slowly clear lactate in a manner quite similar to findings in fish, other amphibians and lizards. Additionally, our findings indicate that lactate metabolism is not highly influenced by season alone, but that intracellular glucose levels may be sensitive to annual patterns.

Comparative analysis of fiber-type composition in the iliofibularis muscle of phrynosomatid lizards (Squamata).

The lizard family Phrynosomatidae comprises three subclades: the closely related sand and horned lizards, and their relatives the Sceloporus group. This family exhibits great variation in ecology, behavior, and general body plan. Previous studies also show that this family exhibits great diversity in locomotor performance abilities; as measured on a high-speed treadmill, sand lizards are exceptionally fast sprinters, members of the Sceloporus group are intermediate, and horned lizards are slowest. These differences are paralleled by differences in relative hindlimb span. To determine if muscle fiber-type composition also varies among the three subclades, we examined the iliofibularis (IF), a hindlimb muscle used in lizard locomotion, in 11 species of phrynosomatid lizards. Using histochemical assays for myosin ATPase, an indicator of fast-twitch capacity, and succinic dehydrogenase, denoting oxidative capacity, we classified fiber types into three categories based on existing nomenclature: fast-twitch glycolytic (FG), fast-twitch oxidative-glycolytic (FOG), and slow-twitch oxidative (SO). Sand lizards have a high proportion of FG fibers (64-70%) and a low proportion of FOG fibers (25-33%), horned lizards are the converse (FG fibers 25-31%, FOG fibers 56-66%), and members of the Sceloporus group are intermediate for both FG (41-48%) and FOG (42-45%) content. Hence, across all 11 species %FOG and %FG are strongly negatively correlated. Analysis with phylogenetically independent contrasts indicate that this negative relationship is entirely attributable to the divergence between sand and horned lizards. The %SO also varies among the three subclades. Results from conventional nested ANCOVA (with log body mass as a covariate) indicate that the log mean cross-sectional area of individual muscle fibers differs among species and is positively correlated with body mass across species, but does not differ significantly among subclades. The log cross-sectional area of the IF varies among species, but does not vary among subclades. Conversely, the total thigh muscle cross-sectional area does not vary among species, but does vary among subclades; horned lizards have slimmer thighs. Muscle fiber-type composition appears to form part of a coadapted suite of traits, along with relative limb and muscle sizes, that affect the locomotor abilities of phrynosomatid lizards.

Effect of activity duration on recovery and metabolic costs in the desert iguana (Dipsosaurus dorsalis).

The majority of elevated O(2) consumption associated with short and vigorous activity occurs during recovery, thus an assessment of associated metabolic costs should also examine the excess post-exercise oxygen consumption (EPOC). This study examined O(2) uptake during exercise, EPOC and distance traveled during 5-, 15-, 60- and 300-s sprints at maximal treadmill intensity in Dipsosaurus (N=10; 74.3+/-2.1 g). EPOC (0.08, 0.14, 0.23 and 0.18 ml O(2) g(-1), respectively) was large (80-99% of total elevated O(2) consumption) and increased significantly between 5 and 60 s. The cost of activity (C(act); ml O(2) g(-1) x km(-1)), intended to reflect the total net costs associated with the activity, was calculated as the total elevated O(2) consumption per unit distance traveled. C(act) decreased with activity duration due to proportionally larger increases in distance traveled relative to EPOC volume, and is predicted by the equation C(act)=14.7 x activity duration (s)(-0.24). The inclusion of EPOC costs provides an ecologically relevant estimate of the total metabolic cost of locomotor activity. C(act) exceeds standard transport costs at all durations examined due to the addition of obligate recovery costs. The differences are large enough to impact energy budget analyses for ectotherms.

Roles of lactate and catecholamines in the energetics of brief locomotion in an ectothermic vertebrate.

We have investigated the magnitude and duration of excess post-exercise oxygen consumption (EPOC) in a lizard following a single bout of vigorous exercise of 5-60 s, common activity durations for many ectothermic vertebrates. Desert iguanas (Dipsosaurus dorsalis) were run for 5 s, 15 s, 30 s, or 60 s. Oxygen consumption (VO2) increased from 0.16 ml O2 g(-1) h(-1) at rest to 1.3-1.6 ml O2 g(-1) h(-1) during 5-60 s of running. EPOC duration increased with activity duration, ranging from 35-63 min. EPOC volume, the excess oxygen consumed post-exercise, doubled from 0.13 ml O2 g(-1) following 5 s of activity to 0.25 ml O2 g(-1) after 60 s. EPOC represented 91-98% of the total metabolic expense of the activity. EPOC durations were always shorter than the period required for lactate removal, illustrating that these two processes are not causally related. Alpha- and beta-adrenergic receptor blockade by phentolamine and propranolol had no effect on resting VO2 but depressed excess post-exercise oxygen consumption volumes 2540%. The extent of catechol stimulation post-exercise may be motivation or stimulus dependent. The data indicate that metabolic elevations post-exercise represent the majority of activity costs in lizards. The study suggests that EPOC of ectothermic vertebrates is sensitive to exercise duration and catecholamine release post-activity, even when activity periods are less than 60 s in duration.

Can energetic expenditure be minimized by performing activity intermittently?

Previous research has shown that the energetic expense per unit distance traveled for one bout of short-duration activity is much greater than the energetic expense associated with long-duration activity. However, animals are often seen moving intermittently, with these behaviors characterized by brief bouts of activity interspersed with brief pauses. We hypothesized that, when multiple bouts of brief activity are performed intermittently, the energetic cost per unit distance is less than when only one short bout is performed. Mice were run 1, 2, 3, 5, 9 or 13 times for 15 s at their maximal speed within a 375 s period while enclosed in an open-flow respirometry system on a treadmill. The mice were also run continuously for 375 s. Following the last sprint and the continuous run, the mice remained in the respirometry chamber until their vO2 reached resting levels. Excess exercise oxygen consumption (EEOC), the excess volume of oxygen consumed during the exercise period, increased from 0.03+/-0.01 to 0.40+/-0.02 ml O2g(-)(1) (mean +/- s.e.m., N=9) with activity frequency. However, the excess post-exercise oxygen consumption (EPOC), or volume of oxygen consumed during the recovery period, was independent of activity frequency (range 0.91-1.16 ml O2g(-)(1)) and accounted for more than 80 % of the total metabolic cost when activity was performed intermittently. Lactate concentration was measured at rest, immediately after running and immediately after recovering from running 1, 5 and 13 times within the 375 s period. After running, [lactate] was significantly higher than resting values, but following recovery, [lactate] had reached resting values. The net cost of activity, C(act), calculated by summing EEOC and EPOC and then dividing by the distance run, decreased significantly from 132+/-38 to 6+/-1 ml O2g(-)(1 )km(-)(1) as activity frequency increased. When these values for C(act) were compared with the cost of running continuously for the same amount of time, the values were identical. Therefore, we conclude that animals can minimize energetic expenditure by performing brief behaviors more frequently, just as they can minimize these costs if they increase the duration of continuous behaviors.

Evidence for facilitated lactate uptake in lizard skeletal muscle.

To understand more fully lactate metabolism in reptilian muscle, lactate uptake in lizard skeletal muscle was measured and its similarities to the monocarboxylate transport system found in mammals were examined. At 2 min, uptake rates of 15 mmol l(-1) lactate into red iliofibularis (rIF) were 2.4- and 2.2-fold greater than white iliofibularis (wIF) and mouse soleus, respectively. alpha-Cyano-4-hydroxycinnamate (15 mmol l(-1)) caused little inhibition of uptake in wIF but caused a 42-54 % reduction in the uptake rate of lactate into rIF, suggesting that much of the lactate uptake by rIF is via protein-mediated transport. N-ethymaleimide (ETH) (10 mmol l(-1)) also caused a reduction in the rate of uptake, but measurements of adenylate and phosphocreatine concentrations show that ETH had serious effects on rIF and wIF and may not be appropriate for transport inhibition studies in reptiles. The higher net uptake rate by rIF than by wIF agrees with the fact that rIF shows much higher rates of lactate utilization and incorporation into glycogen than wIF. This study also suggests that lactate uptake by reptilian muscle is similar to that by mammalian muscle and that, evolutionarily, this transport system may be relatively conserved even in animals with very different patterns of lactate metabolism.

Activity before exercise influences recovery metabolism in the lizard Dipsosaurus dorsalis.

During recovery from even a brief period of exercise, metabolic rate remains elevated above resting levels for extended periods. The intensity and duration of exercise as well as body temperature and hormone levels can influence this excess post-exercise oxygen consumption (EPOC). We examined the influence of activity before exercise (ABE), commonly termed warm-up in endotherms, on EPOC in the desert iguana Dipsosaurus dorsalis. The rate of oxygen consumption and blood lactate levels were measured in 11 female D. dorsalis (mass 41.1 +/- 3.0 g; mean +/- s.e.m.) during rest, after two types of ABE and after 5 min of exhaustive exercise followed by 60 min of recovery. ABE was either single (15 s of maximal activity followed by a 27 min pause) or intermittent (twelve 15 s periods of exercise separated by 2 min pauses). Our results indicate that both single and intermittent ABE reduced recovery metabolic rate. EPOC volumes decreased from 0.261 to 0.156 ml of oxygen consumed during 60 min of recovery when lizards were subjected to intermittent ABE. The average cost of activity (net V(O2) during exercise and 60 min of recovery per distance traveled) was almost 40 % greater in lizards that exercised without any prior activity than in lizards that underwent ABE. Blood lactate levels and removal rates were greatest in animals that underwent ABE. These findings may be of particular importance for terrestrial ectotherms that typically use burst locomotion and have a small aerobic scope and a long recovery period.

The effects of intensity on the energetics of brief locomotor activity.

The energetic costs associated with locomotion are often estimated only from the energy expended during activity and do not include the costs incurred during recovery. For some types of locomotion, this method overlooks important aspects of the metabolic costs incurred as a result of the activity. These estimates for energetic cost have also been predicted from long-duration, low-intensity activities that do not necessarily reflect all the behavior patterns utilized by animals in nature. We have investigated the effects of different activity intensities on the metabolic expenditure (per unit distance traveled) associated with brief exercise, and offer a more inclusive analysis of how the energetics of short-duration activities might be analyzed to estimate the costs to the animal. Mice ran on a treadmill for 15 or 60 s at 25 %, 50 % or 100 % of maximum aerobic speed (MAS) while enclosed in an open-flow respirometry system. Following the run, each mouse was allowed to recover while remaining enclosed in the respirometry chamber. Excess exercise oxygen consumption (EEOC), the excess volume of oxygen consumed during the exercise period, increased with the duration and increased linearly with the intensity of exercise. In contrast, the volume of oxygen consumed during the recovery period, or excess post-exercise oxygen consumption (EPOC), was independent of exercise intensity and duration and accounted for more than 90 % of the total metabolic cost. The net cost of activity (C(act)), calculated by summing EEOC and EPOC and then dividing by the distance run, increased as both activity duration and intensity decreased. The values for C(act) ranged from 553 ml O(2 )g(-)(1 )km(-)(1) for a 15 s run at 25 % MAS to 43 ml O(2 )g(-)(1 )km(-)(1) for a 60 s run at 100 % MAS. Combining these data with data from a companion paper, we conclude (1) that EPOC is independent of both the duration and intensity of activity when exercise duration is brief in mice, (2) that EPOC accounts for a majority of the oxygen consumed as a result of the activity when exercise durations are short, and (3) that animals can minimize their energy expenditure per unit distance by running faster for a longer period.

The roles of acidosis and lactate in the behavioral hypothermia of exhausted lizards.

We conducted this study to determine whether two of the physiological changes associated with non-sustainable exercise, elevated blood lactate levels and decreased arterial pH, contribute to the behavioral hypothermia exhibited by exhausted lizards. Dipsosaurus dorsalis were placed in a thermal gradient and their body temperatures were recorded from 08:00 to 14:00 h. At 14:00 h, animals were subjected to different experimental regimens. In the exercise (E) regimen, animals at 40 degrees C were forced to exercise maximally for 5 min on a treadmill. In the lactate (L) regimen, animals were infused with 11.5 ml kg-1 of 250-500 mmol l-1 sodium lactate. In the osmolarity control (O) regimen, animals were injected with 11.5 ml kg-1 of 500 mmol l-1 NaCl, and in the injection control (I) regimen, animals were injected with 11.5 ml kg-1 of 150 mmol l-1 NaCl. In the hypercapnia (H) regimen, the thermal gradient was flushed with a gas mixture containing 10 % CO2, 21 % O2 and 69 % N2, a treatment that lowers the arterial pH of D. dorsalis to a value comparable with that imposed by exhaustive exercise. A group of control (C) animals was left undisturbed in the thermal gradient for 24 h. Animals in all experimental groups were returned to the thermal gradient, and their cloacal temperatures were monitored until 08:00 h the following morning. The mean cloacal temperature of E animals underwent a significant decrease of 4-7 degrees C, relative to control animals, which persisted for 7 h. The mean cloacal temperatures of animals subjected to 2 h of regimen H also decreased by 3.5-9 degrees C and remained depressed for 12 h following the beginning of the treatment. L, O and I animals did not undergo a significant change in body temperature following treatment, and their mean body temperatures did not differ from those of C animals at any time during the experiment. The results of this study suggest that the metabolic acidosis, but not the elevated blood lactate level, that follows exhausting exercise might play a role in the behavioral hypothermia that follows exhausting exercise in D. dorsalis.

EPOC and the energetics of brief locomotor activity in Mus domesticus.

Excess post-exercise oxygen consumption (EPOC) is normally not considered in determinations of the metabolic cost of activity. This approach overlooks an important energetic cost that an animal incurs as a result of activity. To examine the importance of EPOC, we determined how the energetic cost of locomotion was affected by activity of short duration and high intensity. Mice were run at maximum speed on a treadmill while enclosed in an open-flow respirometry system. After sprinting for 5, 15, 30, or 60 sec, each mouse was allowed to recover while remaining enclosed in the respirometry chamber. Exercise oxygen consumption (EOC), the volume of oxygen consumed during the exercise, increased linearly with sprint duration. EPOC was determined as the volume of oxygen consumed after exercise ended until rest was reached. EPOC volumes were found to be constant following 5-60 sec of activity and accounted for > or = 90% of the total metabolic cost. The average EPOC volume of all treatments was 0.76 +/- 0.456 ml O2.gm-1. The net cost of activity (Cact), which considers both EOC and EPOC, decreased as sprint duration increased and varied between 500 ml O2.g-1.km-1 for 5 sec to 30 ml O2.g-1.km-1 for 60 sec of activity. The values for Cact were 15 to 250 times higher than traditional estimates of locomotor costs. From these data, it can be concluded that (1) EPOC is not affected by short exercise durations; (2) EPOC is an important energetic consideration when exercise durations are short; and (3) the metabolic costs of brief, vigorous locomotion may be much higher than previously estimated.

The influence of corticosterone and glucagon on metabolic recovery from exhaustive exercise in the desert iguana Dipsosaurus dorsalis.

The skeletal muscles of ectothermic vertebrates possess an elevated glyconeogenic capacity that is responsible for a major portion of lactate removal and glycogen resynthesis following exercise. In lizards, changes in plasma hormone levels and the influence of differing hormone levels on muscle metabolism postexercise are poorly understood. We measured the effects of 5 min of exhaustive exercise on plasma levels of glucagon and corticosterone in the desert iguana Dipsosaurus dorsalis. We also determined the extent to which these hormones influence, or are influenced by, postexercise plasma lactate concentrations postexercise. Exercise resulted in the accumulation of 20 mM blood lactate, while plasma glucose levels remained stable throughout 90 min of recovery. Plasma glucagon was elevated sevenfold during 5 min of exercise and returned to resting levels within 45 min of recovery. Glucagon stimulated lactate incorporation into glycogen in isolated red muscle fiber bundles. Plasma corticosterone was also elevated to three times normal resting values, but only after 45 min of recovery. Blocking corticosterone elevation with metyrapone did not alter the kinetics of plasma lactate removal. In lizards, the dramatic rise in plasma glucagon occurs at the same time as previously reported elevated skeletal muscle glyconeogenesis and elevated glucagon stimulates lactate removal in vitro, strongly suggesting a role for glucagon in postexercise skeletal muscle metabolism.

Postexercise thermoregulatory behavior and recovery from exercise in desert iguanas.

Desert iguanas (Dipsosaurus dorsalis) undergo respiratory recovery more rapidly and incur lower energetic costs when they recover from 40 degrees C burst activity at 20 degrees C than when they recover at 40 degrees C. However, a body temperature of 20 degrees C falls well outside the preferred activity temperature range of this species, and imposes several physiological and behavioral liabilities. To determine if exhausted animals would favor a thermal regimen that allows for rapid and inexpensive respiratory recovery, we exercised lizards to exhaustion and allowed them to recover in a laboratory thermal gradient for 180 min. Recovering animals allowed their body temperatures to cool significantly to a mean temperature of 33.5 degrees C during the first 60 min of recovery, and subsequently rewarmed themselves to an average temperature of 38 degrees C for the remainder of their recovery period. Control animals maintained a constant body temperature of 37.7 degrees C throughout the 180-min recovery period. We then exercised animals to exhaustion at 40 degrees C and allowed them to recover for 180 min under a thermal regimen that mimicked that selected by exhausted animals in the previous experiment. Animals recovering under this thermal regimen returned to rates of O2 consumption, removed exercise-generated blood lactate, and incurred energetic costs that were more similar to data previously collected for animals recovering from exercise at a constant 40 degrees C than to data from animals recovering at 20 degrees C. These results suggested that the energetic benefits associated with recovery at 20 degrees C are not of sufficient biological importance to cause a major shift in thermoregulatory behavior.

Regulation of skeletal muscle metabolism in the lizard Dipsosaurus dorsalis by fructose-2,6-bisphosphate.

Changes in liver and skeletal muscle fructose-2,6-bisphosphate (Fru-2,6-P2) concentrations were compared during fasting, exercise, and recovery in the lizard Dipsosaurus dorsalis and in outbred mice (Mus musculus). We present the first correlative evidence that suggests that a decrease in the content of Fru-2,6-P2 may mediate elevated gluconeogenesis in lizard skeletal muscle. Contents of Fru-2,6-P2 in lizard gastrocnemius and red and white iliofibularis (IF) were significantly lower (as much as 55% in white IF) during recovery from exhaustive exercise than at rest. Recovery from exhaustive exercise had no significant effect on Fru-2,6-P2 concentrations in any mouse muscle examined. Fasting significantly depressed lizard and mouse liver Fru-2,6-P2 contents and decreased lizard red IF by over 84% from the fed condition. Lizard red and white muscle fiber bundles incubated in 20 mM lactate had significantly lower Fru-2,6-P2 (94 and 61% depression, respectively) than those incubated in 8.5 mM glucose. These results are consistent with the hypothesis that Fru-2,6-P2 acts as a signal for controlling gluconeogenesis in lizard skeletal muscle.

Hormonal regulation of hepatic gluconeogenesis: influence of age and training.

The contributions of three major gluconeogenic regulators, glucagon (10(-7) M), alpha-adrenergic agonist phenylephrine (10(-5) M), and beta-agonist isoproterenol (10(-5) M) to hepatic glucose synthesis in liver slices from Fischer 344 rats were examined in relation to age and endurance training. Young (4 mo), middle-aged (12 mo), and old (22 mo) male Fischer 344 rats (n = 66) were divided into trained or sedentary groups. Trained animals were run 10 wk on a treadmill at 75% of maximal capacity, 1 h/day, 5 days/wk. Animals were killed at rest, and sections of liver were removed and sliced in a tissue microtome. Slices were incubated in L-[U-14C]lactic acid, Ringer solution, and one of the aforementioned gluconeogenic regulators. Rates of lactate incorporation into glucose and glycogen were significantly greater in young compared with old animals for all three regulators in both trained and untrained animals. Training elicited a 35, 52, and 63% improvement in lactate incorporation into glucose compared with untrained when the livers of young (16.9 +/- 1.2 vs. 10.9 +/- 1.1 mumol.g protein-1.min-1), middle-aged (12.8 +/- 1.3 vs. 6.1 +/- 1.2 mumol.g protein-1.min-1), and old (11.2 +/- 1.1 vs. 4.1 +/- 0.6 mumol.g protein-1.min-1) animals, respectively, were incubated in glucagon. Rates with phenylephrine followed a similar pattern to that with glucagon across age and training, but absolute rates were significantly lower. No training effect in gluconeogenic rate was found when liver was incubated in the presence of isoproterenol. It is concluded that the gluconeogenic capacity of liver declines with age regardless of the gluconeogenic regulator and that training was able to partially offset age-related declines in glucagon-stimulated and alpha-receptor-mediated gluconeogenesis.

Post-exercise lactate metabolism: a comparative review of sites, pathways, and regulation.

Most vertebrates utilize supplemental lactate production to support the energetic demands of vigorous, brief exercise. Despite similar patterns of accumulation, there appears to be a trichotomy with regards to lactate processing post-exercise. Most fish retain most of their lactate intramuscularly, using it for in situ glycogen replenishment. Recent evaluation of fish muscle concludes that pyruvate kinase reversal is a probable gluconeogenic pathway. Amphibians and reptiles also utilize lactate as a muscle glyconeogenic substrate, but lactate is not sequestered post-exercise. None of these groups utilize hepatic gluconeogenesis to any significant extent post-exercise, and muscle glucose uptake is limited. Lactate oxidation plays a major role post-exercise in mammals, with hepatic and muscular gluco- and glyconeogenesis contributing to a lesser extent. Glucocorticoids may regulate lactate release from fish muscle, although catecholamines may influence glyconeogenesis in reptile muscle. Insulin affects lactate metabolism indirectly through its effects on muscle glucose metabolism.

Maximal sprint speeds and muscle fiber composition of wild and laboratory house mice.

We compared males from four groups of house mice (Mus domesticus), all bred and raised under common conditions in the laboratory: randombred Hsd:ICR; a wild population from Wisconsin; hybrids from lab dams; hybrids from wild dams. Wild mice were much faster sprinters (maximal forced sprint speeds over 1.0 m ranged from 2.38 to 3.34 m/s) than were lab mice (range = 0.89-1.68 m/s). Hybrids exhibited intermediate speeds (range = 1.54-2.70 m/s) and body masses, indicating largely additive inheritance. Type-specific mean muscle fiber cross-sectional areas of the gastrocnemius muscle did not differ significantly among groups. Percentage cross-sectional areas occupied by each of the three identified fiber types also did not differ significantly among groups, nor did they covary with body mass. For their body mass, however, lab mice had smaller gastrocnemius muscles than did wild and hybrid mice, which had muscles of similar size. Although we cannot rule out the possibility that smaller gastrocnemius muscles or slight differences in fiber composition account for the lower sprint speeds of the lab mice, we suggest that differences in unmeasured physiological, behavioral or motivational factors are probably the primary cause. This interpretation is supported by a lack of correlation between individual differences in sprint speed and either relative gastrocnemius muscle mass or muscle fiber type composition.

Role of norepinephrine in hepatic gluconeogenesis: evidence of aging and training effects.

This study examined the relationship among the sympathetic neurotransmitter norepinephrine (NE), hepatic gluconeogenesis, and glyconeogenesis in 63 (30 trained and 33 untrained) young (7 mo), middle-aged (15 mo), and old (25 mo) male Fischer 344 rats. Animals were trained 1 h/day, 5 days/wk for 10 wk at treadmill speeds of 75% of age-specific maximal capacity. Liver sections, removed at rest, were sliced and incubated in [14C]lactic acid and 0, 0.5, 1.0, 3.0, or 6.0 ng/ml NE. The rate of [14C]lactate incorporation into glucose was significantly greater in young compared with old animals in both training groups and at all NE concentrations. All trained animals had greater rates of glucose production from lactate than their untrained counterparts at 0.5, 1.0, 3.0, and 6.0 ng/ml NE. At each NE concentration, the old rats showed the lowest rates of glycogen synthesis from lactate. The untrained rats in all age groups were the least responsive to increases in NE concentration. Total hepatic glycogen synthase activity exhibited age-related declines as the young and middle-aged had significantly greater total activity compared with the old animals: 620.4 +/- 27.5, 590.0 +/- 37.9, and 436.3 +/- 44.5 disintegrations/min, respectively. No differences with training were found in total activity. The percent of glycogen synthase in the active form was significantly greater in young compared with old in both the trained (48.6 +/- 2.0 vs. 40.0 +/- 1.3% active) and untrained animals (44.7 +/- 2.2 vs. 35.4 +/- 1.5% active).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of endurance training on the age-related decline in hepatic glyconeogenesis.

Hepatic gluconeogenic and glyconeogenic capabilities were investigated in Fischer 344 rat livers (ages 7, 15 and 25 months; n = 66) to determine if endurance training affected age related decrements in these hepatic functions. Animals were trained 1 h/day, 5 days/week for 10 weeks at treadmill speeds of 75% of age-specific maximal capacity. After training, rats were injected (300 mg/kg) with a known gluconeogenic inhibitor, 3-mercaptopicolinic acid (MPA). Two endurance tests were performed to help assess the contribution of gluconeogenesis to exercise performance, an initial test 4 days prior to injection and a final test immediately post-injection. MPA significantly (P < 0.05) reduced running times in all trained groups compared to their control test: 89%, 81%, and 51% in the young, middle-aged, and old, respectively. MPA reduced running times in the untrained animals 19%, 11%, and 8%, respectively. Three days after the last exercise bout, the animals were anesthetized and liver sections were sliced and incubated in [14C]lactic acid or [14C]fructose. An age-related decline was found in [14C]lactate incorporation (middle-aged decreases 66%, old decreases 54%) and in [14C]fructose incorporation (middle-aged decreases 51%, old decreases 48%) into glycogen. Differences existed in lactate incorporation in trained compared to untrained animals for the young, middle-aged, and old groups: 150.1 +/- 11.3 vs. 102.1 +/- 10.0; 75.3 +/- 6.2 vs. 34.9 +/- 6.4; and 69.3 +/- 14.9 vs. 47.0 +/- 4.7 nmol/g/h, respectively. No differences were found with training in any of the age groups for fructose. Phosphoenolpyruvate carboxykinase (PEPCK) activity and messenger RNA (mRNA) were significantly reduced in the old compared to the young rats (decreases 64% and decreases 58%, respectively). No training effects were found for either PEPCK activity or mRNA for any age group. These results suggest that hepatic gluconeogenic and glyconeogenic capabilities declined with age. Training had an effect in attenuating the glyconeogenic decline but had a minimal effect in offsetting the age-related decline in PEPCK.