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Biomedical subjects

L Ekman

Publications and source records attributed to L Ekman.

At least 55 records · Page 3Linked to original sources
PubMed1984

Whole-body tyrosine flux in relation to energy expenditure in weight-losing cancer patients.

Whole-body tyrosine flux was measured in seven weight-losing cancer patients and compared with that of seven noncancer patients with malnutrition. L[U-14C] tyrosine was infused intravenously (IV) after an overnight fast under resting conditions and flux rates, oxidation, and incorporation into proteins of tyrosine were calculated from plateau values of specific activity of tyrosine in plasma and of labeled expired carbon dioxide. Rates of protein synthesis were calculated from the flux rate of tyrosine after subtracting the proportion oxidized. Simultaneous measurements of whole-body carbon dioxide production and oxygen uptake were also performed in each subject. Cancer patients had elevated whole-body tyrosine flux, protein synthesis, and energy expenditure when expressed in relation to body weight and whole-body potassium while the differences in tyrosine kinetics became of borderline significance when expressed in relation to energy expenditure. Tyrosine incorporation into whole-body proteins corresponded to a synthesis rate of 2.70 +/- 0.17 protein/kg/d in cancer patients and 2.18 +/- 0.17 in control patients (P less than 0.025). The results show that elevated protein synthesis in weight-losing cancer patients may explain not more than one third of the elevated energy expenditure. Therefore, other systems that utilize energy must increase in activity.

Aged↗
PubMed1984

Gluconeogenesis in tumor-influenced hepatocytes.

The growth of a tumor leads to alterations in host carbohydrate metabolism. In this study we examined gluconeogenic capacity and amino acid transport in tumor-influenced and control rat hepatocytes. Serum glucose level decreased with increasing tumor burden and a significant correlation (r = -0.80) was observed. Hepatic glycogen content was similar in both groups after an overnight fast. Endogenous glucose production was 27% higher in tumor-influenced hepatocytes. The presence of 10mM of alanine led to 72% stimulation of gluconeogenesis in tumor-influenced hepatocytes as compared to 48% stimulation in control hepatocytes. The same trends were present when lactate was used as a substrate. Alanine transport into the cells was increased in tumor-influenced hepatocytes by 55% +/- 5% at a physiologic level of substrate. In conclusion, gluconeogenesis from alanine and lactate is significantly increased in tumor-influenced hepatocytes despite decreased serum glucose levels. This is associated with increased gluconeogenic capacity and accelerated alanine transport.

Alanine↗
PubMed1984

Resting energy expenditure in malnourished patients with and without cancer.

Resting energy expenditure was measured in a heterogeneous group of weight-losing cancer patients (n = 28) in comparison with noncancer patients with (n = 26) and without (n = 17) weight loss. Energy expenditure was measured in a ventilated hood after an overnight fast. The results are presented in relationship to the nutritional state of the patients. Cancer patients had elevated energy expenditure compared to noncancer patients when compared on several different bases. The slopes of the regressions between the degree of malnutrition and energy expenditure differed between cancer and noncancer patients. Depleted cancer patients had similar resting energy expenditure as predicted for healthy well-nourished individuals, but significantly higher compared with hospitalized malnourished noncancer patients. However, the differences in resting energy expenditure seemed to be less pronounced when very severely depleted cancer and noncancer patients were compared. The results indicate that a small but statistically significantly elevated energy expenditure occurs in a considerable number of cancer patients. It may, therefore, add to weight loss due to anorexia, but anorexia is considered to be quantitatively the more important factor of the two.

Aged↗
PubMed1983

Activities of key enzymes in relation to glucose flux in tumor-host livers.

1. Isotope and non-isotope methods were used to study hepatic metabolism of glucose in tumor-host livers. 2. Glycogen synthase, phosphofructokinase activities (Vmax) were decreased, while glucose-6-phosphate dehydrogenase and lactate dehydrogenase activities were increased in tumor-host livers. 3. Glycogen phosphorylase, glucokinase and several mitochondrial enzymes, had normal maximum activity in tumor-host livers. Net flux of glucose was decreased in the Embden-Meyerhof and the pentose phosphate pathway in tumor animals. 4. The hepatic cycling of glucose-carbons in tumor animals was significantly decreased as shown by different [14C] [3H] ratios of radioactivity in RNA and lactate, determined from simultaneous incorporation of [U-14C]glucose and [2-3H]glucose. 5. This study demonstrates that previous reports of increased activities of rate limiting enzymes of glucose metabolism in tumor-host livers do not represent a general finding of high glucose metabolism in tumor-host livers.

Animals↗
PubMed1983

Evaluation of oxidative metabolism in tumour-host livers as a possible cause of energy loss in cachectic sarcoma-bearing mice.

Oxygen consumption has been measured in sarcoma-bearing mice, liver cells and tumour tissue. The aim was to determine whether oxidative metabolism in tumour-host livers contributes to the negative energy balance in non-growing animals with a tumour due to insufficient hepatic adaptation of energy consumption. The oxygen uptake in isolated liver cells from freely fed and starved sarcoma-bearing mice showed a 50% decrease (depressed by 322 mumol O2/hr/g) compared to freely fed controls, while starvation of control animals reduced the oxygen uptake in the liver cells by 30-40%. In host tissues other than the liver, total oxygen uptake was depressed by an average 27% (depressed by 50 mumol O2/hr/g) 10-11 days after tumour implantation. In freely fed animals the ratio between oxygen uptake in the tumour-host liver and the host was 0.13 and 0.18 in sarcoma-bearing and control mice respectively. Depression of oxidative metabolism in tumour-host livers was not associated with ultrastructural alterations in the mitochondria or in other cellular organelles studied by electron microscopy. It is concluded that the negative energy balance in a non-growing tumour-bearing host is not explained by deficient adaptation of the hepatic oxidative metabolism, and that depression of activity metabolism in tumour-bearing animals accounts for depression of the metabolic rate in host tissues other than the liver.

Animals↗
PubMed1983

Isolation of mouse liver cells: perfusion technique and metabolic evaluation.

A procedure has been developed for isolation of intact mouse liver cells by collagenase perfusion. Mouse livers were perfused in situ via the heart. The cell metabolism was evaluated as respiratory activity and protein synthesis. The results agree with those which have been reported for isolated rat liver cells. A shortcoming was the low yield of liver cells obtained per animal. The procedure described here seems to offer a convenient means by which it is possible to obtain isolated mouse liver cells which are appropriate for acute metabolic experiments.

Animals↗
PubMed1983

Metabolic response of whole body and peripheral tissues to enteral nutrition in weight-losing cancer and noncancer patients.

This study evaluated whether or not the efficiency of utilizing energy substrates and nitrogen differs among cancer and control patients during enteral feeding. Oxygen uptake and glucose, lipid, and amino acid metabolism across the leg were measured in cancer patients who had lost approximately 18% of their body weight and were compared with that of patients without cancer with similar body-weight loss. Metabolic balances across the leg were evaluated relative to food intake, energy expenditure, energy balance, nitrogen balance, and urinary excretion of urea, creatinine, adrenaline, and noradrenaline. All measurements were performed twice in each patient: first in the fasted state and second during nutrition after 14 days of a controlled enteral infusion of a formula diet of 35 kcal/kg . day. Quantitative measurements of metabolism across the leg before and after 14 days of enteral nutrition were compared with changes in nutritional status. Whole body utilization of energy and of nitrogen were not significantly different among cancer patients and controls, whereas the simultaneously measured net balances of glycerol and free fatty acids across the leg of cancer patients were statistically significantly more negative during the constant infusion of the formula diet. The results in this study emphasize that malnourished cancer patients are quite comparable with patients with benign malnutrition in terms of whole body and peripheral metabolism both before and in the response to enteral feeding.

Aged↗
PubMed1983

Lack of evidence for elevated breakdown rate of skeletal muscles in weight-losing, tumor-bearing mice.

Protein degradation was measured as tyrosine release rate from proteins of extensor digitorum longus (EDL) muscles and as urinary excretion of 3-methylhistidine in freely fed adult nongrowing C57BL/6J mice with sarcomas, to study protein degradation in cancer-induced wasting of skeletal muscles. Whole muscle protein breakdown rate was unchanged, whereas protein synthesis was depressed, leading to an increased net degradation of skeletal muscles with loss of soluble, myofibrillar, and collagen proteins. Starvation for 24 hours elevated whole muscle protein breakdown in mice with and without sarcomas. Subsequent refeeding for 24 hours normalized the degradation. Adaptation to anorexia in pair-fed controls was achieved by a decrease in muscle protein turnover evaluated by urinary excretion of 3-methylhistidine over 5 days. The measurement of "catabolic decrease" of muscle protein breakdown protected the muscle mass in mice without tumors, but it was ineffective in tumor-bearing animals. The unchanged rate of breakdown of proteins in whole EDL muscles from tumor-bearing mice was accompanied by increased maximum cathepsin D activity and by elevated autolytic activity at acid pH in some muscles. Therefore, cathepsin D activity and net protease activities did not reflect whole muscle protein degradation in tumor-induced malnutrition. The results demonstrate that wasting of skeletal muscles in experimental cancer was not dependent on increased degradation but was dependent on depressed protein synthesis.

Animals↗
PubMed1983

Energy metabolism in nongrowing mice with sarcoma.

The time course of energy metabolism has been studied in weight-stable and nongrowing mice with a transplantable methylcholanthrene-induced sarcoma. Daily oxygen consumption and carbon dioxide production were measured in relation to the tumor growth from the time of tumor implantation. The time course of energy dynamics was related to the end-state changes in body composition. Freely fed sarcoma-bearing mice decreased their whole-body energy expenditure in proportion to the tumor growth. This was due to the accompanying anorexia. The alteration in oxygen consumption and carbon dioxide production was continuously evident 24 hr/day in sarcoma-bearing mice. The tumor-bearing mice lost body fat and had decreased respiratory quotient, while pair-fed controls maintained their body composition, and their respiratory quotients agreed with the food respiratory quotient. Loss of body lipids in freely fed sarcoma-bearing mice reflected a negative energy balance, accompanied with increased fat oxidation, while maintenance of body composition in pair-fed controls reflected a decreased metabolic rate. Sarcoma-bearing mice showed a significantly higher energy expenditure in relation to their food intake compared to that of pair-fed controls. Estimates of partition of oxygen uptake in sarcoma-bearing mice support that both the host and the tumor account for the elevated energy expenditure. This study has confirmed a small but significantly increased energy expenditure in sarcoma-bearing mice, which was continuously present 24 hr/day in spite of unlimited availability of food. This illustrates the fatal outcome of experimental cancer.

Animals↗
PubMed1982

Glucose turnover, gluconeogenesis from glycerol, and estimation of net glucose cycling in cancer patients.

A double isotope method was used in patients with progressive malignancy and in control patients to measure: glucose turnover, conversion rate of carbon skeleton of glycerol into glucose, and the interorgan cycling of glucose carbons (Cori-cycle plus alanine-glucose cycle). [U-14C]glycerol and [6-3H]glucose were given intravenously as a single dose injection. The time course of the specific radioactivities of [6-3H] and [U-14C]glucose was followed in blood. The pool size and the turnover rate of glucose were increased in the cancer group as compared with the control patients. The net recycling of glucose carbons was not increased in the cancer group, despite the increased turnover of glucose. The alterations in the metabolism of glucose did not correlate with the plasma levels of insulin or thyroid hormones (T4, T3, rT3) neither in the entire cancer group nor in those cancer patients who were repeatedly investigated at different intervals of time. The turnover rate of glucose in the cancer patients correlated inversely to their body weight index. The gluconeogenesis rate, given as the fractional conversion rate of the injected radioactive dose of [14C]glycerol, or as mol glucose . kg body weight-1 . day-1, was increased in the cancer group, but still contributed only 3% of the glucose turnover rate in both cancer and control patients. We conclude that an increased gluconeogenesis from glycerol is not significant in terms of energy expenditure in patients with progressive malignancy, as has previously been concluded for the gluconeogenesis from alanine. It seems that increased turnover of glucose may contribute to inappropriately high energy expenditure in cancer patients.

Adult↗
PubMed1982

Reutilization of amino acid carbons in relation to albumin turnover in nongrowing mice with sarcoma.

Reutilization of amino acid carbons was evaluated in relation to increased turnover of albumin in tumor-bearing mice. A methylcholanthrene-induced sarcoma (MCG 101) was used in nongrowing mice (C57BL/6J). Sarcoma-bearing mice developed hypoalbuminemia, but pair-fed controls did not. The hypoalbuminemia was caused by increased albumin degradation rate, measured by injection of Na214CO3, and by exponentially increased deposition of albumin into the tumor compartment. The fractional synthesis rate of albumin was doubled in tumor-bearing mice compared with controls. The translational capacity of albumin synthesis evaluated in vitro was maintained in tumor host livers. The recycling of [14C]leucine carbons was almost extinguished in plasma albumin of sarcoma-bearing mice, while that of control mice contributed to 30 to 40% of the total leucine carbon flux in turned over albumin. The recycling of arginine carbons was also different when measured after simultaneous injection of [guanido-14C]arginine and [2,3-3H]arginine. The hepatic pool of free leucine was increased by 22% in tumor-bearing mice. It is concluded that increased albumin degradation in cancer may be a disordered event and is earlier and of initially greater quantitative importance than is altered synthesis of albumin for the development of hypoalbuminemia in experimental cancer.

Amino Acids↗
PubMed1981

Protein degradation in human skeletal muscle tissue: the effect of insulin, leucine, amino acids and ions.

1. The protein degradation rate of human skeletal muscle was evaluated in vitro in isolated fibre bundles from the rectus abdominus muscle by measuring the tyrosine released from muscle tissue proteins. Protein metabolism in this semi-intact preparation was compared with that of the intact extensor digitorum longus muscles from rats under the same experimental conditions. 2. Protein balance was negative in both preparations, but protein synthesis and degradation were two to three times higher in the rat muscles. Tyrosine was released at a constant rate for at least 3 h of incubation independent of whether protein synthesis was inhibited or not. Disintegration of the muscle fibres more than doubled the tyrosine release rate. Human red gastrocnemius muscle showed 37% higher degradation rate compared with the predominantly white rectus abdominus muscle. The half-life of human skeletal muscle protein in vitro was estimated to be 20 days when calculated from the rate of tyrosine release. 3. The addition of leucine to the incubation medium decreased the rate of protein degradation, which was further decreased by the addition of other amino acids. Insulin did not influence the protein degradation rate during 2 h of incubation. This did not reflect a lack of sensitivity to insulin of the preparation, since protein synthesis responded to insulin. Calcium (5 mmol/l) stimulated and zinc (0.1 mmol/l) inhibited the protein degradation. 4. This experimental system may be suitable as an additional tool for evaluating protein degradation in human skeletal muscles.

Adult↗
PubMed1981

Evaluation of anorexia as the cause of altered protein synthesis in skeletal muscles from nongrowing mice with sarcoma.

The importance of decreased food intake as the mechanism behind altered protein metabolism in skeletal muscle in cancer was evaluated. A methylcholanthrene-induced sarcoma (MCG 101) transplanted in weight-stable and nongrowing mice (C57BL/6J) was used as the tumor-animal model. Three study groups with appropriate control groups were used: sarcoma-bearing mice; pair-fed mice; and starved mice. The synthesis of myofibrillar and sarcoplasmic proteins was decreased in sarcoma-bearing mice. This was correlated to decreased content of RNA in the muscles and caused a net loss of muscle tissue was measured by dry weight of skeletal muscles. The incorporation rate of amino acids into myofibrillar and sarcoplasmic proteins was decreased to the same extent in the pair-fed mice as that in the sarcoma-bearing mice. This probably reflected decreased protein synthesis, since the radioactivity (dpm/mg) did not differ significantly in the crude transfer RNA fraction between the groups. Separation of soluble proteins from muscle tissue by means of ion-exchange chromatography showed that the pattern of decreased protein synthesis was not tumor specific when compared to muscle affected by starvation. The decrease in protein synthesis was more or less selective, since the synthesis of basic proteins was considerably decreased and was influenced more than were neutral and acidic proteins in both cancer and starvation. Anorexia of a tumor-bearing host is a sufficient trigger to induce decreased protein synthesis in skeletal muscles, but other factors may also be of quantitative importance.

Animals↗
PubMed1981

Metabolism in peripheral tissues in cancer patients.

Cancer patients have increased insulin resistance in skeletal muscles and probably also in the liver. The insulin production in response to a glucose challenge is decreased. This is associated with decreased glucose uptake in peripheral tissues and increased gluconeogenesis from amino acids, lactate, and glycerol. The correlation between the insulin response to a glucose challenge and the activities of glycolytic and oxidative rate-limiting enzymes in muscle tissue suggests a common denominator for these metabolic alterations. The most prominent feature in alteration of lipid metabolism is a reduction of body fat, probably dependent on increased lipolysis. The released fatty acids are oxidized outside the tumor mass. Species characteristics may be important for the degree of hyperlipidemia. Wasting of the skeletal muscle mass is caused by decreased protein synthesis and probably increased degradation. Anorexia can induce but not entirely explain this altered protein metabolism. Decreased physical activity may be another important factor for the depressed protein synthesis. Total parenteral nutrition (TPN) improves the muscle protein synthesis. The mechanism behind increased fractional degradation of muscle proteins in vitro is not clear, but it may be coupled to increased cathepsin D activity.

Animals↗