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Biomedical subjects

M N Goodman

Publications and source records attributed to M N Goodman.

At least 55 records · Page 3Linked to original sources
PubMed1983

Glucose uptake and insulin sensitivity in rat muscle: changes during 3-96 weeks of age.

It has been demonstrated that aging diminishes the rate of glucose utilization by rat skeletal muscle. To determine the basis for this occurrence as well as its temporal sequence, glucose utilization was examined in isolated hindquarters of 3-, 5-, 8-, 16-, 24-, 48-, and 96-wk-old male Sprague-Dawley rats. Glucose utilization diminished progressively during early development (3-5 wk) and adolescence (5-16 wk) in hindquarters perfused in the absence of added insulin. At the same time there was a progressive shift of the insulin dose-response curve to the right, indicating diminished insulin sensitivity and a marked decrease in maximum insulin responsiveness. In contrast, between 24 and 96 wk of age, insulin sensitivity and the rate of glucose utilization in the absence of added insulin did not decrease, and there was only a small decrease in maximum responsiveness. The rate-limiting step in glucose utilization under all conditions was glucose transport. Even at high insulin concentrations, free glucose was not detected in the muscle cells of young or old rats, the uptake of 2-deoxyglucose diminished in parallel with that of glucose, and there was no evidence of a defect in glucose metabolism. These findings indicate that in the Sprague-Dawley rat glucose transport into skeletal muscle and in particular its sensitivity and responsiveness to insulin diminish progressively during early development and adolescence. No further marked changes occurred up to at least 96 wk of age. To what extent these early age-associated changes are due to insulin binding and to what extent to alterations in the glucose transport system per se remains to be determined.

Aging↗
PubMed1982

Muscle glucose metabolism following exercise in the rat: increased sensitivity to insulin.

Muscle glycogen stores are depleted during exercise and are rapidly repleted during the recovery period. To investigate the mechanism for this phenomenon, untrained male rats were run for 45 min on a motor-driven treadmill and the ability of their muscles to utilize glucose was then assessed during perfusion of their isolated hindquarters. Glucose utilization by the hindquarter was the same in exercised and control rats perfused in the absence of added insulin; however, when insulin (30-40,000 muU/ml) was added to the perfusate, glucose utilization was greater after exercise. Prior exercise lowered both, the concentration of insulin that half-maximally stimulated glucose utilization (exercise, 150 muU/ml; control, 480 muU/ml) and modestly increased its maximum effect. The increase in insulin sensitivity persisted for 4 h following exercise, but was not present after 24 h. The rate-limiting step in glucose utilization enhanced by prior exercise appeared to be glucose transport across the cell membrane, as in neither control nor exercised rats did free glucose accumulate in the muscle cell. Following exercise, the ability of insulin to stimulate the release of lactate into the perfusate was unaltered; however its ability to stimulate the incorporation of [(14)C]glucose into glycogen in certain muscles was enhanced. Thus at a concentration of 75 muU/ml insulin stimulated glycogen synthesis eightfold more in the fast-twitch red fibers of the red gastrocnemius than it did in the same muscle of nonexercised rats. In contrast, insulin only minimally increased glycogen synthesis in the fast-twitch white fibers of the gastrocnemius, which were not glycogen-depleted. The uptake of 2-deoxyglucose by these muscles followed a similar pattern suggesting that glucose transport was also differentially enhanced. Prior exercise did not enhance the ability of insulin to convert glycogen synthase from its glucose-6-phosphate-dependent (D) to its glucose-6-phosphate-independent (1) form. On the other hand, following exercise, insulin prevented a marked decrease in muscle glucose-6-phosphate, which could have diminished synthase activity in situ. The possibility that exercise enhanced the ability of insulin to convert glycogen synthase D to an intermediate form of the enzyme, more sensitive to glucose-6-phosphate, remains to be explored. These results suggest that following exercise, glucose transport and glycogen synthesis in skeletal muscle are enhanced due at least in part to an increase in insulin sensitivity. They also suggest that this increase in insulin sensitivity occurs predominantly in muscle fibers that are deglycogenated during exercise.

Animals↗
PubMed1981

Dichloroacetate: effects on exercise endurance in untrained rats.

The effect of dichloroacetate (DCA), an activator of pyruvate dehydrogenase, on the performance of fed, untrained rats was evaluated while swimming for different durations. DCA-treated rats were able to swim almost 40% longer than controls (354 plus or minus 18 sec, p less than .001). This was associated with lower levels of blood and muscle lactate at rest and after 210 and 240 sec of swimming. At exhaustion, blood lactate was the same in the two groups even though the DCA rats had worked for an additional 99 sec (16.9 plus or minus 1.2 versus 15.8 plus or minus 1.2 mM/L NS). Pretreatment with DCA did not alter the usual exercise-induced decreases in muscle ATP and creatine phosphate or liver glycogen. After 210 sec of exercise, plasma FFA and blood glucose and acetoacetate were also the same in the two groups; however, beta-hydroxybutyrate was somewhat higher, and there was a small but significant sparing of muscle glycogen in te DCA group. The data indicate that DCA enhances the ability of rats to exercise at near maximal work loads. They are consistent with the notion that improved endurance is a consequence of a decreased rate of lactate accumulation; however, the possibility that it is secondary to some other action of DCA cannot be excluded.

3-Hydroxybutyric Acid↗
PubMed1981

Insulin binding and sensitivity in rat skeletal muscle: effect of starvation.

In contrast to adipose tissue and heart, the in vitro sensitivity of skeletal muscle to insulin is enhanced by starvation. To determine the basis for this, insulin binding and its ability to stimulate glucose metabolism were examined in the incubated rat soleus. In solei from 50-g rats, starvation for 48 h enhanced insulin binding by 50-100% at concentrations of 100 ng/ml or less. Starvation also resulted in higher basal and insulin-stimulated rates of glycogen synthesis, glycolysis, and glucose uptake. The enhanced effect of insulin only occurred at concentrations less than 50-75 ng/ml, in keeping with the increased binding of insulin in this concentration range. On the other hand, under conditions in which binding at equilibrium was the same, glucose uptake was still higher in the starved group, suggesting that some postreceptor event may have been more sensitive to insulin. These studies confirm that the in vitro sensitivity of rat skeletal muscle to insulin is enhanced by 48 h of starvation. They suggest that this is due at least partially to an increase in insulin binding at physiological concentrations.

Animals↗
PubMed1981

Adaptation to prolonged starvation in the rat: curtailment of skeletal muscle proteolysis.

Previous studies have established that 16-wk-old nonobese and obese rats conserve body protein during prolonged starvation. To determine the basis for this, protein synthesis and degradation in skeletal muscle were evaluated in the isolated perfused hindquarters of these rats, in the fed state and when starved for 2, 5, 10, and 11 days. Rats aged 4 and 8 wk were used as a comparison. The results indicate that the response to starvation depends on several factors: the age of the rat, its degree of adiposity, and the duration of the fast. An early event in starvation was a decline in muscle protein synthesis. This occurred in all groups, albeit this reduction occurred more slowly in the older rats. A later response to starvation was an increase in muscle proteolysis. This occurred between 2 and 5 days in the 8-wk-old rats. In 16-wk-old rats it did not occur until between 5 and 10 days, and it was preceded by a period of decreased proteolysis. In 16-wk-old obese rats, a decrease in proteolysis persisted for upwards of 10 days and the secondary increase was not noted during the period of study. The data suggest that the ability of older and more obese rats to conserve body protein during starvation is due, in part, to a curtailment of muscle proteolysis. This adaptation seems to correlate with the availability of lipid fuels.

Aging↗
PubMed1980

Oxygen consumption in perfused skeletal muscle. Effect of perfusion with aged, fresh and aged-rejuvenated erythrocytes on oxygen consumption, tissue metabolites and inhibition of glucose utilization by acetoacetate.

1. O2 consumption, glucose metabolism and the energy status of skeletal muscle were compared in isolated rat hindquarters perfused with aged (21--35 days), fresh and aged-rejuvenated human erythrocytes. 2. The age of the erythrocytes did not affect O2 consumption, glucose utilization or lactate release either at rest or during exercise. The concentrations of ATP, phosphocreatine and lactate within the muscle were also unaffected by the use of aged erythrocytes. 3. Perfusion with acetoacetate did not inhibit glucose utilization; but, it caused a marked increase in the tissue concentration of citrate in the soleus, a slow-twitch red muscle, and a smaller increase in the gastrocnemius, which contains fast-twitch red and white fibres. Results were similar in hindquarters perfused with aged and aged-rejuvenated erythrocytes. 4. These findings suggest that perfusion with aged human erythrocytes does not cause major alterations in the metabolic performance of the isolated rat hindquarter.

Acetoacetates↗
PubMed1980

Starvation in the rat. I. Effect of age and obesity on organ weights, RNA, DNA, and protein.

Previous studies have shown that obese man adapts to prolonged starvation with a conservation of body protein. In an attempt to delineate the biochemical and hormonal changes responsible for this adaptation, the effect of starvation was studied in rats with differing abilities to survive a fast and conserve protein. Sixteen-week-old rats made obese by fat feeding survived starvation for 25-30 dys, whereas 16-wk-old controls survived 11-12 days and the 8-wk-old controls for 6-7 days. Starvation decreased hepatic weight, RNA, and protein early in the fast in all three groups. In heart, the extensor digitorum longus muscle and some other organs decreases in RNA, protein, and weight occurred more slowly and were smaller in magnitude in the 16-wk-old control and obese rats. A pronounced loss of cardiac protein and RNA occurred in the 8-wk-old group. We conclude that 16-wk-old control and obese rats are better able to survive and conserve organ protein and RNA during prolonged starvation than younger rats. To what extent this reflects differences in the age and to what extent differences in adiposity remains to be determined.

Age Factors↗
PubMed1980

Starvation in the rat. II. Effect of age and obesity on protein sparing and fuel metabolism.

Sixteen-week-old control and obese rats survive longer than 8-wk-old control rats. In addition, unlike the 8-wk-old group, they conserve tissue RNA and protein. To evaluate the basis for this, the effects of starvation on circulating fuels and hormones and the urinary excretion of nitrogen and 3-methylhistidine (3MH) were compared in the three groups. Urinary nitrogen and 3MH diminished during prolonged starvation in 16-wk-old obese and control rats, suggesting that both groups are able to conserve protein and curtail muscle proteolysis. In contrast, urine nitrogen and 3MH did not decrease in 8-wk-old control rats. Protein conservation in the older rats was associated with diminished blood levels of alanine and increased levels of lipid fuels, ketone bodies, and free fatty acids. Although ketone bodies and free fatty acids were also increased during the first few days of starvation in 8-wk-old rats, there was no evidence of protein sparing. In all groups, as fat stores became exhausted terminally, blood lipid levels decreased and protein catabolism increased. Starvation caused insulin to decrease to comparable levels in all rats; however, minimal levels were reached later in the older groups. Thyroxine and triiodothyronine (T3) decreased during the fast in both control groups; however, T3 did not decrease in the obese rats. These findings support the contention that the conservation of protein during prolonged starvation requires the continued availability of lipid fuels. The role of insulin and thyroid hormone in modulating these adaptations is unclear.

Aging↗
PubMed1979

Insulin sensitivity of rat skeletal muscle: effects of starvation and aging.

The effects of starvation and of aging on the sensitivity of skeletal muscle to insulin were studied in the isolated perfused rat hindquarter preparation. As we have shown previously, starvation for 48 h had no effect on glucose uptake in hindquarters perfused with high levels of insulin (5 and 20 mU/ml). On the other hand, in the presence of physiological concentrations of insulin (50--200 muU/ml), glucose utilization was substantially greater in starved rats. Low concentrations of insulin had a greater effect on glucose uptake in fed young (100-g) than in fed older (350-g) rats. Starvation for 48 h enhanced glucose uptake in both young and older rats; however, the relative differences persisted. Starvation had similar effects on glucose utilization by the incubated soleus and extensor digitorum longus muscle. In addition, it augmented the stimulation by insulin of alpha-aminoisobutyric acid transport into the incubated extensor digitorum longus muscle. These results suggest that the in vitro sensitivity of skeletal muscle to physiological concentrations of insulin is enhanced during starvation. The basis for these findings and their physiological implications remain to be determined.

Aging↗
PubMed1978

The purine nucleotide cycle in skeletal muscle.

The following evidence demonstrates that ammonia production in muscle occurs via the reactions of the purine nucleotide cycle: i) Extracts of cytosol which lack glutamine dehydrogenase produce ammonia under conditions that mimic muscle doing work. In such extracts a member of the purine nucleotide cycle (AMP, IMP, or adenylosuccinate) must be present in order that ammonia production can take place, ii) Perfused hindleg of rat or hindleg in situ produces ammonia during exercise, and there is a concomitant production of IMP and adenylosuccinate. Exercise causes a decrease in the contents of glutamate, aspartate, and glutamine and an increase in the content of alanine of perfused hindleg of rat. However, output of alanine does not change or is diminished during exercise. Glutamine output is diminished by exercise. Epinephrine increases the output and tissue content of ammonia and glutamine. It decreases the output and content of alanine, and it decreases the contents of aspartate and glutamate.

Adenosine Diphosphate↗
PubMed1977

The purine nucleotide cycle. Studies of ammonia production by skeletal muscle in situ and in perfused preparations.

Ammonia production by hind limbs of rat was studied in perfused preparations during rest, exercise, and hypoxia, and while the perfusate contained epinephrine or cyanide. Ammonia production by hind limbs was also studied in situ during rest and exercise. Strong correlations were observed between ammonia, IMP, and lactate formation. Adenylosuccinate was not present in detectable amounts in resting muscle (less than 1 nmol/g dry weight) but it appeared and rose sharply in exercising muscle, and then declined during recovery. The maximum found was about 18 nmol/g dry weight. When IMP accumulation exceeded 2.8 mumol/g dry weight, the formation of adenylosuccinate diminished, presumably because of an inhibition of adenylosuccinate synthetase by excess substrate. Exercise resulted in a greatly increased output of ammonia and a decreased output of alanine and glutamine. The tissue contents of aspartate and glutamate were decreased, while that of alanine was increased. The content of malate increased 3-fold during exercise. Epinephrine, hypoxia, and cyanide each caused an increased output of ammonia at the expense of the amino acid content of the tissue. These results provide evidence for the operation of the purine nucleotide cycle in skeletal muscle under various conditions that are associated with an increased rate of glycolysis.

Adenosine Monophosphate↗