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Biomedical subjects

N B Ruderman

Publications and source records attributed to N B Ruderman.

At least 109 records · Page 6Linked to original sources
PubMed1981

Diabetes and exercise.

This review describes (1) the metabolic and hormonal response to exercise in normal and diabetic man, and (2) the potential benefits of physical training in diabetes. Whereas in normal man plasma glucose varies little during exercise, the insulin-dependent diabetic subject may experience an increase in plasma glucose, a modest decrease or a marked decrease which can result in symptomatic hypoglycemia. Evidence is reviewed that the glycemic response depends on the ambient plasma concentration of insulin and that this may be influenced by an effect of exercise on the absorbtion of insulin from its site of injection. The response to exercise of noninsulin-dependent diabetic subjects and of diabetic subjects with autonomic neuropathy is also described. Physical training improves glucose tolerance in some noninsulin-dependent diabetic subjects and in insulin-dependent patients, it may diminish insulin requirements. It may also have a role in retarding the development of cardiovascular complications. Physical training is not totally innocuous, however, and in many patients with diabetes special precautions are required.

Diabetes Mellitus↗
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

The "metabolically-obese," normal-weight individual.

A great many disorders including maturity-onset (type II) diabetes, hypertension, and hypertriglyceridemia are frequently associated with adult-onset obesity and improve with caloric restriction. It is the premise of this brief review that there are patients with these disorders who are not obese according to standard weight tables or other readily-available criteria; but who would also respond favorably to caloric restriction. It is proposed that such individuals might be characterized by hyperinsulinism and possibly an increase in fat cell size compared to patients of similar age, height, and weight and/or to themselves at an earlier time. The possibility is also discussed that inactivity is a contributing factor in some of these individuals and that for them, the appropriate therapy might be exercise.

Adipose Tissue↗
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↗
PubMed1981

Regulation of ornithine decarboxylase in skeletal muscle: evidence for the involvement of an insulin-dependent serum factor.

Previous studies in vivo have shown that the activity of ornithine decarboxylase (ODC), the rate-controlling enzyme in polyamine biosynthesis, is markedly decreased in muscle of diabetic rats and is restored to normal by insulin therapy. Also, muscle ODC is diminished by starvation and increased by refeeding. To investigate the basis for these findings, the regulation of ODC was studied in vitro using rat soleus and extensor digitorum longus muscles. Incubation of muscles from fed rats in Krebs-Henseleit solution resulted in a 75% decrease in ODC activity within 1 h. Addition of insulin and amino acids had no effect; however, 50% rat serum increased ODC activity four- to seven-fold after the initial decrease. Rat serum also increased ODC in muscles from starved rats. The effect of serum was blocked by both cycloheximide and antinomycin D. Serum from diabetic rats was only 50% as effective as serum from normal rats in increasing ODC activity. Addition of physiologic levels of insulin to diabetic serum had no effect; however, treatment of diabetic rats with insulin in vivo restored serum activity to normal. These findings suggest that insulin modulates the synthesis of ODC via production of a second circulating factor, the activity of which is diminished in serum of diabetic rats. They also suggest that the stimulation of polyamine biosynthesis by this factor may be an integral component of the growth-promoting effect of insulin on muscle in vivo.

Animals↗
PubMed1980

Ornithine decarboxylase activity in insulin-deficient states.

The activity of ornithine decarboxylase, the rate-controlling enzyme in polyamine biosynthesis, was determined in tissues of normal control rats and rats made diabetic with streptozotocin. In untreated diabetic rats fed ad libitum, ornithine decarboxylase activity was markedly diminished in liver, skeletal muscle, heart and thymus. Ornithine decarboxylase was not diminished in a comparable group of diabetic rats maintained on insulin. Starvation for 48h decreased ornithine decarboxylase activity to very low values in tissues of both normal and diabetic rats. In the normal group, refeeding caused a biphasic increase in liver ornithine decarboxylase; there was a 20-fold increase in activity at 3h followed by a decrease in activity, and a second peak between 9 and 24h. Increases in ornithine decarboxylase in skeletal muscle, heart and thymus were not evident until after 24-48h of refeeding, and only a single increase occurred. The increase in liver ornithine decarboxylase in diabetic rats was greater than in normal rats after 3h of refeeding, but there was no second peak. In peripheral tissues, the increase in ornithine decarboxylase with refeeding was diminished. Skeletal-muscle ornithine decarboxylase is induced more rapidly when meal-fed rats are refed after a period without food. Refeeding these rats after a 48h period without food caused a 5-fold increase in ornithine decarboxylase in skeletal muscle at 3h in control rats but failed to increase activity in diabetic rats. When insulin was administered alone or together with food to the diabetic rats, muscle ornithine decarboxylase increased to activities even higher than in the refed controls. In conclusion, these findings indicate that the regulation of ornithine decarboxylase in many tissues is grossly impaired in diabetes and starvation. They also suggest that polyamine formation in vivo is an integral component of the growth-promoting effect of insulin or some factor dependent on insulin.

Animals↗
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↗