Biomedical subjects

G D Cartee

Publications and source records attributed to G D Cartee.

50 records · Page 3Linked to original sources

PubMed1990

Exercise increases susceptibility of muscle glucose transport to activation by various stimuli.

The insulin sensitivity of glucose transport in skeletal muscle is enhanced after exercise. In this study, stimulation of transport of the nonmetabolizable glucose analogue 3-O-methylglucose by the insulin-mimetic agents vanadate and H2O2 was markedly enhanced in rat epitrochlearis muscles 18 h after a bout of swimming. This increase in susceptibility of the glucose transport process in muscle to stimulation by insulin-mimetic agents that act beyond the insulin-binding step provides evidence that the increased insulin sensitivity results from an effect of exercise on a later step in the activation of glucose transport. Hypoxia and insulin appear to stimulate glucose transport by different pathways in muscle as evidenced by an additivity of their maximal effects. The effect of a submaximal hypoxic stimulus on muscle sugar transport was greatly amplified 3 h after exercise. This increase in susceptibility of glucose transport to stimulation by hypoxia after exercise suggests that the increased sensitivity is not limited to the insulin sensitive pathway. In contrast to exercise (i.e., swimming), in vitro muscle contractions did not result in an increase in sensitivity of muscle glucose transport to insulin, raising the possibility that a humoral factor is necessary for this effect.

3-O-Methylglucose↗

PubMed1990

Reversal of enhanced muscle glucose transport after exercise: roles of insulin and glucose.

Exercise stimulates insulin-independent glucose transport in skeletal muscle and also increases the sensitivity of the glucose transport process in muscle to insulin. A previous study [D. A. Young, H. Wallberg-Henriksson, M. D. Sleeper, and J. O. Holloszy. Am. J. Physiol. 253 (Endocrinol. Metab. 16): E331-E335, 1987] showed that the exercise-induced increase in glucose transport activity disappears rapidly when rat epitrochlearis muscles are incubated for 3 h in vitro in the absence of insulin and that 7.5 microU/ml insulin in the incubation medium apparently slowed the loss of enhanced sugar transport. We examined whether addition of insulin several hours after exercise increases glucose transport to the same extent as continuous insulin exposure. Addition of 7.5 microU/ml insulin 2.5 h after exercise (when glucose transport has returned to basal levels) increased sugar transport to the same level as that which resulted from continuous insulin exposure. This finding provides evidence for an increase in insulin sensitivity rather than a slowing of reversal of the exercise-induced increase in insulin-independent glucose transport activity. Glucose transport was enhanced only at submaximal, not at maximal, insulin concentrations. Exposure to a high concentration of glucose and a low insulin concentration reduced the exercise-induced increase in insulin-sensitive glucose transport. Incubation with a high concentration of 2-deoxy-D-glucose (2-DG) did not alter the increase in insulin sensitivity, even though a large amount of 2-DG entered the muscle and was phosphorylated.(ABSTRACT TRUNCATED AT 250 WORDS)

3-O-Methylglucose↗

PubMed1989

Effects of aging and exercise on insulin action in rat adipocytes are correlated with changes in fat cell volume.

The effects of exercise on insulin action were evaluated in epididymal adipocytes from 9-mo and 26-mo-old rats. Exercised animals were given voluntary access to running wheels at 6 mo of age. Comparisons were made among these animals, freely eating sedentary rats, and sedentary animals maintained at body weights comparable to those of the runners. When expressed as percentage changes, the responses to insulin, in terms of stimulation of both [U-14C]glucose oxidation and 14C-labeled lipid accumulation, were largest in fat cells from the runners, followed by the paired-weight adipocytes, and the cells from the freely eating sedentary animals. However, the absolute changes in the rates of glucose oxidation and 14C-labeled lipid synthesis produced by insulin were comparable among the different groups. Basal rates of oxidation and 14C-labeled lipid accumulation were directly correlated with average cell size, independent of the treatment group, whereas the percentage increases in these processes produced by insulin were inversely correlated with cell size. Little, if any, effect of age or exercise was observed that could not be attributed to the average fat cell volume.

Adipose Tissue↗

PubMed1989

Prolonged increase in insulin-stimulated glucose transport in muscle after exercise.

Exercise can induce short-term increases in the sensitivity and responsiveness of skeletal muscle glucose transport to insulin. The purpose of this study was to determine the effect of carbohydrate deprivation on the persistence of increased insulin sensitivity and responsiveness after a bout of exercise. Three hours after a bout of exercise, epitrochlearis muscles from carbohydrate-deprived (fat fed) rats showed a 25% greater increase in 3-O-methylglucose (3-MG) transport in response to a maximal insulin stimulus compared with muscles of nonexercised rats; this increase in insulin responsiveness had reversed 18 h postexercise. Muscles of rats fed carbohydrate showed no increase in insulin responsiveness 3 h after exercise. The effect of 60 microU/ml of insulin on 3-MG transport was approximately twofold greater in muscles studied 3 h after exercise than in nonexercised controls regardless of dietary carbohydrate intake. This increase in insulin sensitivity was lost within 18 h in carbohydrate-fed rats but persisted for at least 48 h in carbohydrate-deprived rats. Muscle glycogen increased approximately 41 mumol/g in the rats fed carbohydrate for 18 h, and only approximately 14.5 mumol/g in the rats fed fat for 48 h, after exercise. The persistent increase in insulin sensitivity after exercise in carbohydrate-deprived rats was unrelated to caloric intake, as muscles of fasted and fat-fed rats behaved similarly.

3-O-Methylglucose↗

PubMed1989

Exercise-induced increase in glucose transporters in plasma membranes of rat skeletal muscle.

A previously developed technique for the isolation of plasma and intracellular membrane fractions from rat skeletal muscle was used to investigate transporter migration after insulin treatment or a bout of exercise (45 min of treadmill). Glucose-inhibitable cytochalasin-B binding was used to estimate the number of glucose transporters. Insulin and exercise caused increases in glucose uptake into the hindlimb muscles of 5- and 3-fold, respectively. Each stimulus also caused a 2-fold increase in the number of glucose transporters in plasma membranes prepared from hindlimb muscles. The insulin-induced increase in plasma membrane transporters was accompanied by a concomitant decrease in transporters from the intracellular pool. In contrast to insulin, there was no concomitant decrease in the number of cytochalasin-B-binding sites in the intracellular membrane fraction from exercised muscles. The ability of both insulin and exercise to increase the number of transporters in the plasma membrane is in accordance with recruitment of transporters as one cause of increased transport activity. However, the inability of exercise to decrease the number of transporters in the insulin-sensitive intracellular pool suggests the existence of either a second recruitable transporter pool or masked glucose transporters in the plasma membrane that are unmasked by the muscle contractile activity.

Animals↗

PubMed1988

Insulin-induced decrease in 5'-nucleotidase activity in skeletal muscle membranes.

Insulin releases inositol phosphoglycans from myocytes in culture [(1986) Science 233, 967-972], which display insulinomimetic activity. Because 5'-nucleotidase is anchored to the membrane through inositol-containing phospholipid glycans, we investigated whether insulin could release the enzyme from the membrane. Membranes prepared from hindquarter muscles of rats perfused with insulin showed a 23% decrease in 5'-nucleotidase activity. Isolated membranes from muscle exposed to insulin in vitro also showed a small but reproducible decrease (9%) in 5'-nucleotidase activity relative to unexposed controls. Phospholipase C from Staphylococcus aureus released 60% of the membrane-bound 5'-nucleotidase. We propose that insulin may activate an endogenous phospholipase C that cleaves phospholipid-glycan-anchored proteins.

5'-Nucleotidase↗

PubMed1988

Exercise training induces glycogen sparing during exercise by old rats.

Glycogen utilization during exercise appears to be related to muscle respiratory capacity. Since the decline in hindlimb muscle respiratory capacity that occurs in rats during old age is eliminated when young and old rats undergo an identical exercise training protocol, liver and gastrocnemius glycogen concentrations were determined in identically trained young and old Fischer 344 rats at rest and immediately after a 30-min run requiring approximately 75% of maximal O2 consumption. These values were also compared with untrained age-matched control animals. The animals, which were 10 or 24 mo old after 6 mo of training, were fasted for 24 h before they were killed. Resting gastrocnemius glycogen did not differ among the groups. After 30 min of running, gastrocnemius glycogen was lower in the untrained than the trained groups and was not different between the trained groups. Resting liver glycogen was lower in the old trained group than the untrained groups but not statistically different from the young trained group. The postrun liver glycogen did not differ among the groups. Estimated gastrocnemius and liver glycogen utilization during exercise was decreased in both trained groups compared with untrained age-matched controls. These results indicate that the training-induced glycogen sparing during exercise of the same relative intensity was not diminished with age in identically trained young and old rats.

Aging↗

PubMed1988

Effects of exercise on cardiac myosin isozyme composition during the aging process.

The effects of aging and exercise on isoforms of cardiac myosin and Ca2+-activated actomyosin adenosinetriphosphatase (ATPase) activity were examined in Fischer 344 rats. Rats were divided into running (R) and age-matched sedentary (S) groups. The groups initiated their exercise program at either 3, 4, or 18 mo of age. Rats were killed at 10, 12, 24, or 27 mo of age. ATPase activity decreased 25% in the S group and 28% in the R group from 12 to 27 mo of age. The myosin isozyme patterns shifted in both S and R groups from a predominantly V1 isozyme form (63.8%) at 10 mo of age to a more equal distribution of isozyme forms at 24 mo (V1, V2, and V3 comprising 40.0, 27.8, and 31.9%, respectively). Age-related shifts in myosin composition occurred despite chronic endurance training at an intensity of approximately 75% maximum O2 consumption. Improvement of cardiac performance through training during aging is not accompanied by attenuating shifts in myosin isozyme composition.

Adenosine Triphosphatases↗

PubMed1988

Muscle glucose transport: interactions of in vitro contractions, insulin, and exercise.

Exercise increases permeability of muscle to glucose. Normally, the effects of exercise and a maximal insulin stimulus on glucose transport are additive. However, the combined effect on rat epitrochlearis muscle permeability to 3-O-methylglucose (3-MG) of a maximal insulin stimulus followed by in vitro contractile activity of 1.24 +/- 0.06 mumol.10 min-1.ml intracellular water-1 was no greater than that of either stimulus alone. We found that this absence of an additive effect was caused by prolonged exposure to an unphysiologically high insulin concentration (20,000 microU/ml for 60 min), which, in addition to stimulating glucose transport, appears to prevent further increases in permeability to glucose. When the treatments were reversed and muscles were first stimulated to contract and then incubated with 20,000 microU/ml insulin, 3-MG uptake (mumol.10 min-1.ml intracellular water-1) increased from a control value of 0.26 +/- 0.03 to 1.80 +/- 0.15, compared with 1.04 +/- 0.06 for contractile activity alone, 1.21 +/- 0.08 for insulin, and 1.88 +/- 0.11 for exercise (swimming) plus insulin. Swimming plus in vitro contractile activity did not have a greater effect than contractile activity alone. Our results provide evidence that 1) the effect of exercise on muscle permeability to glucose is mediated solely by a process associated with contractile activity, and 2) it is advisable to avoid the use of unphysiologically high insulin concentrations in studies designed to elucidate in vivo actions of insulin.

3-O-Methylglucose↗

PubMed1987

Endurance training effects on striatal D2 dopamine receptor binding and striatal dopamine metabolite levels.

We have previously shown that endurance training is associated with higher binding of [3H]spiperone to striatal D2 dopamine (DA) receptors of presenescent (21 months old) rats. In the present study we investigated the effects of 6 months of endurance training of young adults on the relationship between steady-state levels of DA and its metabolites in striatum and the affinity and density of striatal D2 DA receptors. The extent of training was confirmed by evaluating the maximal oxygen consumption (VO2 max) in the subjects. D2 DA binding was significantly increased at each of 3 [3H]spiperone concentrations in the young runners. A 'synaptic coupling ratio' calculated as the specific DA binding/DOPAC concentration was significantly increased in runners for the 0.1 and 0.4 nM radioligand concentrations. Across experimental groups levels of DA were highly and positively correlated with specific DA binding at the 0.1, 0.2 and 0.4 nM [3H]spiperone concentrations. Together, these results suggest that exercise can alter the number of DA binding sites and the metabolism of DA in young adult animals.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1987

Muscle respiratory capacity and VO2 max in identically trained young and old rats.

Old rats have a decreased hindlimb muscle respiratory capacity and whole-body maximal O2 consumption (VO2 max). The decline in spontaneous physical activity in old rats might contribute to these age-related changes. The magnitude of the age-related decline is not uniform in all skeletal muscle respiratory enzymes, and the decrease in palmitate oxidation is particularly great. This study was designed to determine if young and old rats subjected to the same exercise-training protocol would attain similar values for VO2 max and several markers of muscle respiratory capacity. Four- and 18-mo-old Fischer 344 rats underwent an identical 6-mo program of treadmill running. After training, both age groups had increased VO2 max above sedentary age-matched controls. However, the old trained rats had a lower VO2 max than identically trained young rats. In contrast to VO2 max, the two trained groups attained similar values for gastrocnemius citrate synthase, cytochrome oxidase, 3-hydroxyacyl-CoA dehydrogenase, palmitate oxidation, and total carnitine concentration. Thus, when the young and old rats performed an identical exercise protocol within the capacity of the old animals, differences in skeletal muscle respiratory capacity were eliminated. The dissimilarity in VO2 max between the identically trained groups was apparently caused by age-related differences in factors other than muscle respiratory capacity.

Aging↗

PubMed1986

Activation of glucose transport in muscle by prolonged exposure to insulin. Effects of glucose and insulin concentrations.

Glucose transport activity was found to increase over 5 h in rat epitrochlearis muscle in response to a moderate concentration (50-100 microunits/ml) of insulin. This process was examined using 3-methylglucose. The increase in permeability to 3-methylglucose was 2- to 4-fold greater after 5 h than after 1 h in muscles incubated with 50 microunits/ml of insulin and 1 or 8 mM glucose. The increase in permeability to 3-methylglucose during the period between 1 and 5 h of exposure to 50 microunits/ml of insulin and 1 mM glucose was due to an increase in the apparent Vmax of sugar transport. There were two components to this activation of glucose transport. One, which was not influenced by inhibition of protein synthesis, resulted in activation of sugar transport to the same extent by 50 microunits/ml as by 20,000 microunits/ml of insulin; however, this activation took approximately 20 times longer with 50 microunits/ml insulin. The other, which was blocked by cycloheximide, resulted in a further activation of sugar transport to a level higher than that attained in response to 20,000 microunits/ml of insulin. Glucose had no effect on activation of sugar transport during the first hour, but a high concentration (20-36 mM) of glucose prevented the further activation of glucose transport during prolonged treatment with 50 microunits/ml of insulin. It appears from these results that prolonged exposure to a moderate concentration of insulin has previously unrecognized effects that include: a progressive activation of glucose transport over a long time that eventually results in as great a response as a "supramaximal" insulin concentration, and in the presence of low glucose concentration, further activation of glucose transport by an additional, protein synthesis-dependent mechanism. The results also show that a high concentration of glucose can, under some conditions, inhibit stimulation of its own transport.

3-O-Methylglucose↗

PubMed1985

Effect of ascorbic acid nutriture on protein-bound hydroxyproline in guinea pig plasma.

This paper provides indirect evidence that ascorbate nutriture affects plasma concentrations of complement component C1q in the guinea pig. C1q is a protein with a hydroxyproline-rich region similar in structure to collagen. It is essential for complement-mediated lysis of pathogens and may also facilitate phagocytic activity of macrophages and neutrophils. Since C1q is the only hydroxyproline-containing protein in the euglobulin fraction of plasma, it can be quantified indirectly by precipitating this fraction, hydrolyzing it and estimating hydroxyproline colorimetrically. We investigated the effect of ascorbate nutriture on protein-bound hydroxyproline (PBH) in the euglobulin fraction of plasma of young male guinea pigs. The animals had been depleted of ascorbate for 3 wk to produce scurvy and then repleted (6 wk) as follows: 0.5, 2.0 and 10.0 mg ascorbate/100 g body weight per d or 10 g ascorbate per liter of drinking water. PBH values were significantly correlated (P less than 0.001) with dietary ascorbate (+ 0.74) and with liver ascorbate (+ 0.75). Plasma PBH was significantly higher (P less than 0.01, Scheffé's test) in guinea pigs fed ample ascorbate (10.0 mg/100 g body weight per day) or tissue-saturating levels (10 g/L of drinking water) than in those fed adequate (2.0 mg/100 g body weight) or suboptimal (0.5 mg/100 g body weight) levels. These data are consistent with the known biochemical role of ascorbic acid in hydroxyproline biosynthesis and suggest a possible link between ascorbate and the immune response via C1q.

Animals↗

PubMedDate not supplied

Cortical elasticity in aging rats with and without growth hormone treatments.

This study quantified the orthotropic elastic changes in cortical bone due to aging as well as determined any elastic changes after acute treatments of growth hormone (GH). Three groups of twenty rats represented three age groups of young adult (9 months), middle age (20 months), and old (31 months) rats. During a ten day period, half of the rats in each age group were given twice-daily doses of recombinant human GH while the remaining half were injected with a vehicle control (saline). The effects of aging and GH on the elastic characteristics of cortical bone were quantified via ultrasonic wave propagation. Propagation velocities of longitudinal and shear waves were measured through cubic cortical specimens from the posterior femoral diaphysis. Density was measured by Archimedes' technique. The normalized, orthotropic elastic properties of Young's moduli (Eii), shear moduli (Gij), and Poisson's ratios (Vij) were calculated and used to compare the groups (where i and j = 1, 2, or 3 reference the radial, circumferential, and longitudinal axes, respectively). Cortical elastic moduli consistently increased with age with the strongest effects demonstrated in radial dependent properties such as E11 (+ 25.3% from 9 to 31 months, p = 0.0004) and G12 (+ 12.6% from 20 to 31 months, p = 0.0419). The ratio of transverse to axial displacement (Poisson's ratio) typically decreased with age (9 to 31 months) as seen in V31 (-24.95%, p = 0.0134) and V32 (-20.7%, p = 0.0015). Overall, a ten day treatment with GH produced no global statistical change in elastic properties (p > 0.05). However, GH did minimize the age related differences that were measured for E22, E33, and V32 between the 9 and 31 month old groups essentially returning old bone to its youthful elastic state. These finding add orthotropic detail to the current understanding of changing cortical elastic properties during aging as well as providing a reference for further studies of GH.

Aging↗