Biomedical subjects

G D Cartee

Publications and source records attributed to G D Cartee.

At least 37 records · Page 2Linked to original sources

PubMed1995

Growth hormone reduces glucose transport but not GLUT-1 or GLUT-4 in adult and old rats.

The primary purpose of this study was to investigate the influence of administration of recombinant-derived human growth hormone (rhGH) to adult male rats of several ages (9, 20, and 31 mo) on skeletal muscle glucose transport. Rats were injected with rhGH (0.7 mg/kg) or vehicle twice daily for 10 days. The rhGH treatment led to a doubling of circulating insulin-like growth factor I levels at each age. Skeletal muscle glucose transport activity was evaluated in isolated epitrochlearis muscle with use of 3-O-methylglucose at three insulin concentrations (0, 100, and 20,000 microU/ml). The results indicate that, after 10 days of rhGH administration, 1) an approximately 20-30% reduction in basal glucose transport activity was evident in muscles from every age group, 2) the ability of a submaximally effective insulin concentration (100 microU/ml) to increase glucose transport activity above basal values was not significantly reduced in any age group, 3) maximal insulin-stimulated glucose transport activity (with 20,000 microU/ml) was significantly reduced (approximately 40%) by rhGH treatment only in the oldest rats, and 4) the alterations in glucose transport activity occurred despite no change in skeletal muscle GLUT-1 or GLUT-4 protein levels.

3-O-Methylglucose↗

PubMed1994

Myocardial glucose transporters and glycolytic metabolism during ischemia in hyperglycemic diabetic swine.

We assessed the effects of 4 weeks of streptozocin-induced diabetes on regional myocardial glycolytic metabolism during ischemia in anesthetized open-chest domestic swine. Diabetic animals were hyperglycemic (12.0 +/- 2.1 v 6.6 +/- .5 mmol/L), and had lower fasting insulin levels (27 +/- 8 v 79 +/- 19 pmol/L). Myocardial glycolytic metabolism was studied with coronary flow controlled by an extracorporeal perfusion circuit. Left anterior descending coronary artery (LAD) flow was decreased by 50% for 45 minutes and left circumflex (CFX) flow was constant. Myocardial glucose uptake and extraction were measured with D-[6-3H]-2-deoxyglucose (DG) and myocardial blood flow was measured with microspheres. The rate of glucose conversion to lactate and lactate uptake and output were assessed with a continuous infusion of [6-14C]glucose and [U-13C]lactate into the coronary perfusion circuit. Both diabetic and nondiabetic animals had sharp decreases in subendocardial blood flow during ischemia (from 1.21 +/- .10 to 0.43 +/- .08 mL.g-1.min-1 in the nondiabetic group, and from 1.30 +/- .15 to 0.55 +/- .11 in the diabetic group). Diabetes had no significant effect on myocardial glucose uptake or glucose conversion to lactate under either well-perfused or ischemic conditions. Forty-five minutes of ischemia resulted in significant glycogen depletion in the subendocardium in both nondiabetic and diabetic animals, with no differences between the two groups. Glycolytic metabolism is not impaired in hyperglycemic diabetic swine after 1 month of the disease when compared with that in normoglycemic nondiabetic animals. The myocardial content of the insulin-regulatable glucose transporter (GLUT 4) was measured in left ventricular biopsies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Glucose transport with brief dietary restriction: heterogenous responses in muscles.

The time course (1, 5, or 20 days) for the effect of dietary restriction (DR; approximately 25% reduction below ad libitum intake) on epitrochlearis and flexor digitorum brevis (FDB) muscle glucose transport activity was studied in female Fischer 344 rats (8 mo old). Epitrochlearis glucose transport activity with 100 microU/ml insulin was increased by 38% after 5 days of DR (P < 0.05) despite no change in glucose transport activity with 0 or 20,000 microU/ml insulin. The increase with 100 microU/ml insulin was not further enhanced by 20 days of DR. DR did not result in a significant increase in the glucose transport activity of the FDB with 0, 100, or 20,000 microU/ml insulin. Abdominal fat content was significantly (P < 0.01) reduced below ad libitum levels only after 20 days of DR. These results demonstrate that DR-induced improvement in epitrochlearis glucose transport activity with a physiological insulin concentration can occur very rapidly, preceding detectable changes in basal or maximal insulin-stimulated glucose transport activity or abdominal fat pad mass, and the enhancement of insulin action does not occur simultaneously in all muscles.

3-O-Methylglucose↗

PubMed1994

Adaptation of muscle glucose transport with caloric restriction in adult, middle-aged, and old rats.

The effects of prolonged caloric restriction (60% of ad libitum intake initiated at 14 wk of age) on glucose transport activity in isolated epitrochlearis muscles were studied in female Fischer 344 rats aged 8, 18, and 23 mo. Basal 3-O-methylglucose transport (3-MG) rate (without insulin) was not significantly altered by caloric restriction. With a submaximally effective insulin concentration (75 microU/ml), 3-MG transport was enhanced in the caloric-restricted groups by 59, 59, and 105% at 8, 18, and 23 mo of age, respectively. With a maximally effective insulin concentration (20,000 microU/ml), 3-MG transport was increased after caloric restriction, despite no change in muscle GLUT4 glucose transporter protein content. These results indicate that chronic caloric restriction enhances insulin stimulation of the glucose transport system independent of changes in basal glucose transport or muscle GLUT4 levels, and insulin-stimulated glucose transport is enhanced in rats with chronic caloric restriction at least until 23 mo of age.

3-O-Methylglucose↗

PubMed1994

Exercise training does not compensate for age-related decrease in myocardial GLUT-4 content.

We assessed the effects of age and endurance exercise training (treadmill running at 75% maximal running capacity, 1 h/day, 5 days/wk for 10 wk) on the total concentration of insulin-regulatable glucose transporters (GLUT-4) and GLUT-4 mRNA levels in the myocardium of male Fischer 344 rats aged 7, 15, and 25 mo. Myocardial GLUT-4 concentration was quantified with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting and detected with a polyclonal antibody to the GLUT-4 transporter. Myocardial GLUT-4 mRNA levels were quantified with slot-blot analysis and a cDNA probe for GLUT-4. Myocardial GLUT-4 concentration in the 25-mo group decreased 27 and 20% compared with the 7- and 15-mo group, respectively (P < 0.0001 and P < 0.003). GLUT-4 mRNA also decreased significantly in the 25-mo group compared with the 7-mo group (20% in the trained and 11% in the untrained group, P < 0.05). Endurance training did not significantly affect myocardial GLUT-4 concentrations in any age group despite a significant increase in GLUT-4 mRNA in the 7- and 25-mo trained groups. In conclusion, myocardial GLUT-4 protein levels in the rat are significantly decreased with age but are unaffected by 10 wk of treadmill running.

Aging↗

PubMed1994

Aging skeletal muscle: response to exercise.

The mass of many weight-bearing muscles declines in old rats, secondary to the atrophy of fibers, particularly of type IIb, with relatively little loss of muscle fibers during most of the adult life span. In humans, muscle atrophy is the result of a combination of progressive fiber loss and fiber atrophy. In both species, the proportion of histochemically determined fiber types is relatively stable across the adult portion of the life span. The loss of strength in old age is predominantly accounted for by reduced muscle mass in humans and rats. Resistance training leads to increased muscle mass and strength in old humans and rats, primarily by increasing fiber CSA. Muscle capillarity is unchanged in old rats but decreases in old dogs. Apparently, capillarity declines in truly sedentary older people. Endurance training enhances capillarity, and old rats and humans can attain levels of capillarity comparable to their active young counterparts, even when performing considerably less exercise. Blood flow during contractile activity is reduced in male rats and humans but not in old female rats or dogs. Oxidative capacity declines in many muscles of sedentary old rats and humans. With endurance training, old individuals from both species attain levels of muscle oxidative capacity quite similar to those in identically training young individuals. Muscle insulin-stimulated glucose transport is enhanced in rats after a bout of exercise, regardless of age. Endurance training elevates muscle GLUT-4 levels in young and middle-aged, but not old, rats, perhaps because the old rats trained at slower treadmill speeds. Middle-aged (47-62 yr) men and women can substantially increase muscle GLUT-4 with relatively brief (12-14 wk) endurance training; older humans (> 70-80 yr) have not been studied. Endurance training leads to reduced LDH activity without altering PFK or phosphorylase in old rats and humans. Muscle glycogen depletion, CP depletion, and lactate accumulation during contractile activity are exaggerated in old rats, apparently secondary to reduced muscle oxidative capacity and blood flow. Resting muscle glycogen concentration is diminished in older humans, probably in part because of a more sedentary lifestyle. Although several months of endurance training raises muscle glycogen concentration in older people, it does not restore it to youthful levels. Endurance training can greatly improve endurance in old age, at least in part by the same mechanism originally described in youth, i.e., an increase in muscle oxidative capacity, which contributes to reduced glycogen depletion.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

PubMed1994

Influence of age on skeletal muscle glucose transport and glycogen metabolism.

Age-related alterations in skeletal muscle carbohydrate metabolism can influence both health and performance. Exercising muscle glycogenolysis is accelerated in old, male rats compared with young animals, perhaps secondary to the age-related reduction in muscle oxidative capacity and blood flow during contractile activity. Muscle oxidative capacity and blood flow during exercise are also reduced in untrained older humans. Endurance training enhances muscle oxidative capacity and promotes muscle glycogen sparing during exercise by young and old rats. Resting muscle glycogen concentration is unchanged in old rats, but considerably reduced in untrained, older humans. Exercise training increases the muscle glycogen levels of older people. The concentration of GLUT-4 glucose transporter protein declines in some muscles of rats during growth and development, but remains stable thereafter. Exercise training can elevate the muscle GLUT-4 protein levels of both young and old humans. On the other hand, exercise training has been shown to increase the GLUT-4 values of adult, but not old rats. After one bout of exercise, muscle sensitivity for insulin-stimulated glucose transport is improved in young and old rats. These findings indicate that several age-related changes in muscle carbohydrate metabolism can be minimized by acute or chronic exercise.

Adult↗

PubMed1993

Myocardial GLUT-4 glucose transporter protein levels of rats decline with advancing age.

Age-related changes in glucose metabolism and glucose transporter protein content have been described in adipose tissue and skeletal muscle, two tissues that express the GLUT-4 isoform of the glucose transporter protein. I studied the effect of age on the levels of GLUT-4 protein in a third insulin-sensitive tissue: the heart. Cardiac ventricles were sampled from male Fischer 344/Brown Norway F1 hybrid (F344/BNNia) rats. The total protein concentration of the left ventricle did not change with age. GLUT-4 levels per mg of protein declined by 15% between 3.5 and 13 months of age, and by another 12% during adulthood (between 13 and 25 months of age); when expressed per g wet weight, the decreases were 13% and 17%, respectively. Linear regression analysis revealed a significant (p < .0001) relationship (r2 = .634) between age and myocardial GLUT-4. These results demonstrate that the GLUT-4 levels in the left ventricle decrease in an age-related fashion and suggest that the capacity for glucose transport might also be reduced.

Aging↗

PubMed1993

Persistent effects of exercise on skeletal muscle glucose transport across the life-span of rats.

Very young rats (< 2 mo) have a persistent increase in insulin-stimulated glucose transport rate in skeletal muscle for several hours after completing a bout of exercise. We studied the effect of exercise on the glucose transport activity of isolated epitrochlearis muscles from male Fischer 344/Brown Norway F1 hybrid rats across a wide range of the life-span (at 3.5, 13, and 25 mo). The stimulation of 3-O-methylglucose (3-MG) accumulation by a submaximally effective insulin concentration (100 microU/ml) was enhanced (50-75%) 4 h after exercise, regardless of age. In contrast, the 3-MG transport rate with 20,000 microU/ml insulin was enhanced after exercise only in the youngest rats (35%), and this increased responsiveness occurred despite no changes in muscle total GLUT-4 levels. In addition, epitrochlearis GLUT-4 levels were reduced by 29% between 3.5 and 13 mo of age in sedentary rats but did not decline further between 13 and 25 mo of age. GLUT-4 levels were moderately but significantly (P < 0.05) related (r = 0.554) to epitrochlearis muscle capacity for insulin-stimulated 3-MG transport.

3-O-Methylglucose↗

PubMed1992

Hypoxia causes glycogenolysis without an increase in percent phosphorylase a in rat skeletal muscle.

Stimulation of skeletal muscle to contract activates phosphorylase b-to-a conversion and glycogenolysis. Despite reversal of the increase in percentage of phosphorylase a after a few minutes, continued glycogen breakdown can occur during strenuous exercise. Hypoxia causes sustained glycogenolysis in skeletal muscle without an increase in percentage of phosphorylase a. We used this model to obtain insights regarding how glycogenolysis is mediated in the absence of an increase in percentage of phosphorylase a. Hypoxia caused a 70% decrease in glycogen in epitrochlearis muscles during an 80-min incubation despite no increase in percentage of phosphorylase a above the basal level of approximately 10%. Muscle Pi concentration increased from 3.8 to 8.6 mumol/g muscle after 5 min and 15.7 mumol/g after 20 min. AMP concentration doubled, attaining a steady state of 0.23 mumol/g in 5 min. Incubation of oxygenated muscles with 0.1 microM epinephrine induced an approximately sixfold increase in percentage of phosphorylase a but resulted in minimal glycogenolysis. Muscle Pi concentration was not altered by epinephrine. Despite no increase in percentage of phosphorylase a, hypoxia resulted in a fivefold greater depletion of glycogen over 20 min than did epinephrine. To evaluate the role of phosphorylase b, muscles were loaded with 2-deoxyglucose 6-phosphate, which inhibits phosphorylase b. The rate of glycogenolysis during 60 min of hypoxia was reduced by only approximately 14% in 2-deoxyglucose 6-phosphate-loaded muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Monophosphate↗

PubMed1992

Diverse effects of calcium channel blockers on skeletal muscle glucose transport.

Verapamil, a calcium channel blocker, inhibited the insulin-stimulated glucose transport rate in isolated rat epitrochlearis muscle in a dose-dependent manner (1-200 microM) without affecting basal glucose transport rate. Verapamil's inhibition was rapid in onset and disappearance; changes in glucose transport rate were detectable when verapamil was added to or removed from the incubation medium 15 min prior to measurement of glucose transport. Verapamil also inhibited the stimulation of muscle glucose transport caused by hypoxia, indicating that the effect was not limited to insulin action. Although the optical isomers of verapamil vary considerably in their potency as Ca2+ channel blockers, they were equally effective inhibitors of insulin-stimulated glucose transport rate. Nifedipine (10-200 microM), a more potent blocker of skeletal muscle Ca2+ channels than verapamil, was less effective as an inhibitor of insulin-stimulated glucose transport. Furthermore, nifedipine (10 microM) did not inhibit hypoxia-stimulated glucose transport. Diltiazem (200 microM), another Ca2+ channel blocker, did not reduce insulin-stimulated glucose transport.

3-O-Methylglucose↗

PubMed1991

Skeletal muscle atrophy in old rats: differential changes in the three fiber types.

This study was undertaken to reevaluate the effects of ageing on skeletal muscle mass and on mitochondrial and glycolytic enzyme levels in the different types of skeletal muscle in rats. It was found that some muscles atrophy with ageing, while others do not, in male rats. Atrophy appears to occur in weight-bearing muscles, and is most marked in those with a high proportion of type IIb fibers. The muscles that did not atrophy are non-weight-bearing, and include the epitrochlearis (predominantly type IIb fibers) and the adductor longus (predominantly type I fibers). The average cross-sectional area of muscle fibers in the plantaris muscles of 28-30-month-old rats was approximately 30% smaller than that of 9-10-month-old animals, providing evidence that the approximately 30% lower weight of the plantaris in the old group was entirely due to fiber atrophy. The proportion of type IIa fibers was decreased and the proportion of type I fibers was increased in the plantaris of the old rats. The respiratory capacity of the soleus muscle (predominantly type I fibers), and the glycolytic capacity of the superficial, white (type IIb) and deep, red (predominantly type IIa) portions of the vastus lateralis, were reduced in the old rats. Our results provide evidence that ageing has differential effects on the three types of skeletal muscle fiber, and on weight-bearing and non-weight-bearing muscles, in the rat.

Aging↗

PubMed1991

Prolonged incubation of skeletal muscle increases system A amino acid transport.

During the course of experiments involving prolonged incubation of skeletal muscle, we observed large increases in system A amino acid transport activity. System A activity was monitored with the nonmetabolizable amino acid analogue alpha-(methylamino)isobutyrate (MeAIB). When rat epitrochlearis muscles are incubated in Krebs-Henseleit buffer supplemented with 0.1% bovine serum albumin and 8 mM glucose, basal MeAIB transport doubles after 5 h and is elevated approximately sevenfold after 9 h compared with rates measured in muscles incubated for 1 h. Insulin-stimulated transport also doubles after 5 h and increases by fourfold after 9 h. The increases in basal and insulin-stimulated system A transport over time can be prevented by incubating muscles in the presence of cycloheximide. Addition of minimum essential medium essential amino acids (EAA) to the incubation medium blocks the increase in basal and insulin-stimulated MeAIB transport measured after 9 h by 85-90 and 60%, respectively. A single amino acid, glutamine, can account for half of the inhibitory effect of EAA on the time-dependent increase in basal system A transport. Amino acid metabolism is not necessary for inhibition of the rise in basal MeAIB transport. At concentrations normally present in minimum essential medium, nonessential amino acids are less effective (51% inhibition) in preventing the rise in basal transport occurring over 9 h. At three times normal concentrations, however, the ability of nonessential amino acids to prevent the time-dependent increases in basal and insulin-stimulated MeAIB transport is comparable to that of EAA. These changes in MeAIB transport with prolonged incubation are not due to muscle deterioration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1991

Prolonged incubation of skeletal muscle in vitro: prevention of increases in glucose transport.

During experiments involving prolonged incubation of skeletal muscle, we observed large increases in glucose transport activity. The basal rate of 3-O-methylglucose (3-MG) transport increased two- to fourfold in rat epitrochlearis muscles incubated for 9 h without insulin in Krebs-Henseleit buffer supplemented with 8 mM glucose. The stimulatory effect of a low concentration of insulin (30 microU/ml, added during the final 30 or 60 min of incubation) on glucose transport activity was enhanced 2.5-fold after 6 h and approximately 5-fold after 9 h of incubation. Exposure of muscles to 100 microU/ml of insulin for the first 8 h inhibited slightly but significantly the increase in insulin-stimulated 3-MG transport over a 9-h incubation period. Incubation of muscles in minimal essential medium (MEM) for 9 h inhibited the time-dependent rise in basal and insulin-stimulated transport by approximately 45%. The effect of MEM was reproduced with MEM essential, but not nonessential, amino acids. Incubation of muscles with MEM plus 100 microU/ml of insulin for the first 8 h prevented the increases in 3-MG transport activity measured after a 9-h incubation period. Muscles incubated for 9 h maintained ATP and phosphocreatine concentrations, and changes in glycogen concentrations were small. Thus we have defined conditions for long-term incubation of skeletal muscle under which a progressive increase in glucose transport is prevented.

Amino Acids↗

PubMed1991

Stimulation of glucose transport in skeletal muscle by hypoxia.

Hypoxia caused a progressive cytochalasin B-inhibitable increase in the rate of 3-O-methylglucose transport in rat epitrochlearis muscles to a level approximately six-fold above basal. Muscle ATP concentration was well maintained during hypoxia, and increased glucose transport activity was still present after 15 min of reoxygenation despite repletion of phosphocreatine. However, the increase in glucose transport activity completely reversed during a 180-min-long recovery in oxygenated medium. In perfused rat hindlimb muscles, hypoxia caused an increase in glucose transporters in the plasma membrane, suggesting that glucose transporter translocation plays a role in the stimulation of glucose transport by hypoxia. The maximal effects of hypoxia and insulin on glucose transport activity were additive, whereas the effects of exercise and hypoxia were not, providing evidence suggesting that hypoxia and exercise stimulate glucose transport by the same mechanism. Caffeine, at a concentration too low to cause muscle contraction or an increase in glucose transport by itself, markedly potentiated the effect of a submaximal hypoxic stimulus on sugar transport. Dantrolene significantly inhibited the hypoxia-induced increase in 3-O-methylglucose transport. These effects of caffeine and dantrolene suggest that Ca2+ plays a role in the stimulation of glucose transport by hypoxia.

3-O-Methylglucose↗

PubMed1990

Recruitment of GLUT-4 glucose transporters by insulin in diabetic rat skeletal muscle.

The cause of reduced insulin-stimulated glucose transport in skeletal muscle of diabetic rats was investigated. Basal and insulin-stimulated glucose uptake into hindquarter muscles of 7-day diabetic rats were 70% and 50% lower, respectively, than in nondiabetic controls. Subcellular fractionation of hindquarter muscles yielded total crude membranes, plasma membranes and intracellular membranes. The number of GLUT-4 glucose transporters was lower in crude membranes, plasma membranes and intracellular membranes, relative to non-diabetic rat muscles. These results were paralleled by reductions in D-glucose-protectable binding of cytochalasin B. Insulin caused a redistribution of GLUT-4 transporters from intracellular membranes to plasma membranes, in both control and diabetic rat muscles. This redistribution was also recorded using binding of cytochalasin B. The insulin-dependent decrement in glucose transporters in intracellular membranes was similar for both animal groups, but the gain and final amount of transporters in the plasma membrane were 50% lower in the diabetic group. The results suggest that insulin signalling and recruitment of GLUT-4 glucose transporters occur in diabetic rat muscle, and that the diminished insulin response may be due to fewer glucose transporters operating in the muscle plasma membrane.

Animals↗

PubMed1990

Exercise induces recruitment of the "insulin-responsive glucose transporter". Evidence for distinct intracellular insulin- and exercise-recruitable transporter pools in skeletal muscle.

Acute exercise, like insulin, increases D-glucose uptake into rat hind limb muscles. Here we examine the distribution of the muscle glucose transporters GLUT-4 and GLUT-1 in plasma membrane and intracellular membrane fractions of skeletal muscle prepared from control, exercised, and acutely insulin-treated rats. Immunoblotting with an anti-GLUT-4 polyclonal antibody showed that acute insulin treatment (by hind limb perfusion or in vivo injection) increased GLUT-4 transporters in a plasma membrane fraction and decreased them in an intracellular membrane fraction. Exercise also increased the GLUT-4 transporters in the plasma membrane, but in contrast to insulin, did not significantly decrease them in the intracellular fraction. Immunoblotting with anti-GLUT-1 antibody revealed that this transporter is largely localized in the plasma membrane. Neither insulin nor exercise significantly increased GLUT-1 transporters in the plasma membrane. The data show that GLUT-4 is an insulin-responsive glucose transporter in skeletal muscle and, furthermore, that GLUT-4 also responds to acute exercise. The results are consistent with recruitment of GLUT-4 glucose transporters to the plasma membrane from intracellular stores. Moreover, exercise-sensitive GLUT-4 transporters do not originate from the insulin-sensitive intracellular membrane fraction, suggesting the existence of distinct intracellular insulin- and exercise-recruitable GLUT-4 transporter pools.

Animals↗

PubMed1990

Exercise modulates the insulin-induced translocation of glucose transporters in rat skeletal muscle.

Insulin and acute exercise (45 min of treadmill run) increased glucose uptake into perfused rat hindlimbs 5-fold and 3.2-fold, respectively. Following exercise, insulin treatment resulted in a further increase in glucose uptake. The subcellular distribution of the muscle glucose transporters GLUT-1 and GLUT-4 was determined in plasma membranes and intracellular membranes. Neither exercise nor exercise----insulin treatment altered the distribution of GLUT-1 transporters in these membrane fractions. In contrast, exercise, insulin and exercise----insulin treatment caused comparable increases in GLUT-4 transporters in the plasma membrane. The results suggest that exercise might limit insulin-induced GLUT-4 recruitment and that following exercise, insulin may alter the intrinsic activity of plasma membrane glucose transporters.

Animals↗