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Biomedical subjects

R Curi

Publications and source records attributed to R Curi.

At least 199 records · Page 11Linked to original sources
PubMed1989

Metabolic changes caused by irregular-feeding schedule as compared with meal-feeding.

In this study rats eating 50% of the quantity of daily food intake observed for free-fed rats were restricted to regular (MF) and irregular intermeal (IF) intervals. Rats which had free access to food (FF) were also included. The experiments were carried out for 1, 2, 3 and 4 weeks. Body weight, daily food intake, stomach fresh weight, blood glucose and free fatty acids (FFA) levels, liver glycogen content and adrenal ascorbic acid were evaluated. The results showed that adaptative metabolic pattern depends on the discipline of the intermeal intervals. Meal-fed rats with a fixed meal time showed better blood glucose maintenance, slower gastric emptying, increased liver glycogen content and lower FFA mobilization during 22-hr fast than the free-fed group. The same amount of food eating by meal-fed rats given randomly in time (IF) promoted a different adaptative metabolic pattern. The results suggest that the regular intermeal period is an important factor for the establishment of the metabolic changes. Therefore, the meal-feeding schedule has to be considered as a particular modality of food restriction.

Adaptation, Physiological↗
PubMed1989

Hyperthyroid-like metabolic changes induced by chronic administration of compound BW 48/80.

The present study examines the metabolic changes caused by chronic mast cell degranulation in rats. Three groups of 5 adult rats each were used: 1) rats treated with increasing doses of BW 48/80 (2 to 6 mg kg-1 day-1, ip, for 4 days); 2) a control group receiving daily saline injections, and 3) rats treated with disodium chromoglycate (DCG) (40 mg kg-1 day-1,ip, for 4 days). The third group was included as a control since DCG blocks mast cell degranulation. Saline- and DCG-treated rats showed little differences except for an increase in spleen wet weight and liver glycogen content in the latter. Chronic treatment with compound BW 48/80 resulted in statistically significant changes such as body weight loss, reduction in thymus and spleen wet weights, decrease in spleen protein content, liver glycogen and blood insulin concentrations, increase in plasma free fatty acids concentration and adrenal wet weight compared to control rats. These metabolic changes are similar to those reported for hyperthyroidism and support previous findings on the possible role of mast cells in the control of thyroid function.

Animals↗
PubMed1989

Pyruvate metabolism by lymphocytes: evidence for an additional ketogenic tissue.

The rate of utilization of pyruvate (at various concentrations) was measured in lymphocytes prepared from rat mesenteric lymph nodes. The quantitative contribution of pyruvate to CO2, lactate, aspartate, alanine, citrate, acetate, acetyl-CoA and ketone bodies accounted for the pyruvate metabolized. Pyruvate utilization was depressed by increasing concentrations of pyruvate. The maximum catalytic activities and selected intracellular distributions of the following enzymes of pyruvate, citrate and acetyl-CoA metabolism were measured: citrate synthase, ATP-citrate lyase, lactate dehydrogenase, acetyl-CoA hydrolase, acetylcarnitine transferase, NAD+- and NADP+- isocitrate dehydrogenases, HMG-CoA lyase, HMG-CoA synthase, Pyruvate dehydrogenase, acetoacetyl-CoA thiolase, 3-oxoacid-CoA transferase, 3-hydroxybutyrate dehydrogenase and pyruvate carboxylase. Acetyl-CoA formed from pyruvate did not contribute to the respiratory energy metabolism of resting lymphocytes. Instead acetyl-CoA was converted to acetoacetate by reactions which may favour the pathway catalyzed by acetoacetyl-CoA thiolase and 3-oxoacid-CoA transferase. Acetate, acetyl- and palmitoyl-carnitine inhibited the decarboxylation of [1-14C] pyruvate. These observations may be connected with the suppression of pyruvate utilization by increased pyruvate substrate concentration. Only very small amounts of either pyruvate or acetate were incorporated into lipids in resting lymphocytes. The amounts incorporated were partitioned in approximately the same pattern into FFA, T.G., cholesterol and cholesterol esters. Taken together the data show that pyruvate metabolism is directed inter alia at the formation of acetoacetate which may serve as a lipid synthesis precursor. When pyruvate utilization and metabolism was enhanced by concanavalin A, then acetoacetate formation was not favoured and from this it is proposed that the acetyl units may then be directed into lipid synthesis and may also make a contribution to the energy metabolism of the activated lymphocyte.

Animals↗
PubMed1989

Effects of aspirin-like drugs on Walker 256 tumor growth and cachexia in rats.

Several studies have shown the relationship between prostaglandins (PGs) and cell proliferation. Some PGs may trigger cell division or are involved in this process. This study analyzes the effect of PG biosynthesis inhibitors on tumor growth in vivo and cachexia in Walker 256 tumor-bearing rats. Indomethacin markedly inhibited tumor growth (95.5%) while ibuprofen and aspirin reduced tumor growth by 73.9% and 59.4%, respectively. In addition, all drug-treated rats partially recovered body weight and food intake as compared to the saline-treated group. These findings suggest that PG synthesis inhibitors improve cancer cachexia.

Animals↗
PubMed1989

Rates of pyruvate utilization and lactate formation by lymphocytes from young and aged rats.

The rates of pyruvate utilization and lactate formation were measured in lymphocytes from young (newly weaned), adult (3-month old) and aged (15-month old) rats. Lymphocytes obtained from mesenteric lymph nodes were incubated at 37 degrees C for 1 h. The conversion of pyruvate to lactate accounted for 92.5% of the total pyruvate utilized by lymphocytes from young rats and was 34.2% and 44.5% for adult and aged rats, respectively. When lymphocytes were stimulated with concanavalin A there was an increase of 65.6% and 37.1% in the rates of pyruvate utilization by lymphocytes from young and adult rats, respectively. No changes in pyruvate utilization were observed in response to concanavalin A in lymphocytes from aged rats.

Aging↗
PubMed1989

The sensitivity of glycogenolysis to glucagon, epinephrine and cyanide in livers from rats in different metabolic conditions.

The action of glucagon, epinephrine and cyanide on hepatic glycogen catabolism in meal-fed rats and the corresponding controls was investigated using the isolated perfused liver. The amounts of glycogen catabolites (glucose, L-lactate and pyruvate) released were correlated with the glycogen content of the livers at the different times after feeding. Irrespective of the metabolic condition, the sensitivity of glycogenolysis to glucagon was roughly proportional to the glycogen content of the livers. However, glycogenolysis in livers from meal-fed rats was less sensitive to epinephrine and cyanide. The difference between meal-fed and controls (ad libitum-fed) was particularly pronounced at 22 hours after feeding. It was concluded that resistance to hepatic glycogen depletion in meal-fed rats during the fasting period may be, partly at least, the consequence of a reduced sensitivity of glycogenolysis to epinephrine and to situations of reduced rates of oxidative phosphorylation.

Animals↗
PubMed1988

Metabolism of pyruvate by isolated rat mesenteric lymphocytes, lymphocyte mitochondria and isolated mouse macrophages.

1. The activities of pyruvate dehydrogenase in rat lymphocytes and mouse macrophages are much lower than those of the key enzymes of glycolysis and glutaminolysis. However, the rates of utilization of pyruvate (at 2 mM), from the incubation medium, are not markedly lower than the rate of utilization of glucose by incubated lymphocytes or that of glutamine by incubated macrophages. This suggests that the low rate of oxidation of pyruvate produced from either glucose or glutamine in these cells is due to the high capacity of lactate dehydrogenase, which competes with pyruvate dehydrogenase for pyruvate. 2. Incubation of either macrophages or lymphocytes with dichloroacetate had no effect on the activity of subsequently isolated pyruvate dehydrogenase; incubation of mitochondria isolated from lymphocytes with dichloroacetate had no effect on the rate of conversion of [1-14C]pyruvate into 14CO2, and the double-reciprocal plot of [1-14C]pyruvate concentration against rate of 14CO2 production was linear. In contrast, ADP or an uncoupling agent increased the rate of 14CO2 production from [1-14C]pyruvate by isolated lymphocyte mitochondria. These data suggest either that pyruvate dehydrogenase is primarily in the a form or that pyruvate dehydrogenase in these cells is not controlled by an interconversion cycle, but by end-product inhibition by NADH and/or acetyl-CoA. 3. The rate of conversion of [3-14C]pyruvate into CO2 was about 15% of that from [1-14C]pyruvate in isolated lymphocytes, but was only 1% in isolated lymphocyte mitochondria. The inhibitor of mitochondrial pyruvate transport, alpha-cyano-4-hydroxycinnamate, inhibited both [1-14C]- and [3-14C]-pyruvate conversion into 14CO2 to the same extent, and by more than 80%. 4. Incubations of rat lymphocytes with concanavalin A had no effect on the rate of conversion of [1-14C]pyruvate into 14CO2, but increased the rate of conversion of [3-14C]pyruvate into 14CO2 by about 50%. This suggests that this mitogen causes a stimulation of the activity of pyruvate carboxylase.

Animals↗
PubMed1988

Glutamine metabolism in isolated incubated adipocytes of the rat.

1. Phosphate-dependent glutaminase activity in the epididymal fat-pad was 15.1 nmol/min per mg of protein. Glutaminase activity demonstrated differences with respect to adipose-tissue sites. Considerable variation was found in different sites of adipose tissue from lean control and Zucker obese animals. 2. Adipocytes incubated in the presence of 2 mM-glutamine utilized glutamine at a rate of 1.8 mumol/h per g dry wt., and glutamate, ammonia, lactate and alanine were produced. Addition of glucose plus insulin increased the rates of glutamine utilization and glutamate, ammonia, lactate and alanine production. Isoprenaline alone or plus glucose further stimulated the rate of glutamine utilization and formation of end products. 3. The rate of incorporation of 14C from glutamine into CO2 was similar to that of glucose, but the rate of incorporation into triacylglycerol was much less. Addition of unlabelled glucose or glucose plus insulin stimulated the rate of incorporation of [14C]glutamine into triacylglycerol, but had no effect on that of 14CO2 formation. Isoprenaline plus glucose increased the rate of incorporation of [14C]glutamine into CO2, but decreased the rate of incorporation into triacylglycerol. 4. In the absence of insulin, the rate of [14C]glutamine incorporation into triacylglycerol was related to the glucose concentration (0-10 mM). However, in the presence of insulin, the rate of incorporation of [14C]glutamine was maximal at 1 mM-glucose.

Adipose Tissue↗
PubMed1988

Does PEPCK play a key role in amino acid oxidation?

The major role of phosphoenolpyruvate carboxykinase (PEPCK) in gluconeogenesis is well known. However, studies on amino acid metabolism indicate that this enzyme may also play an important role in complete oxidation of amino acids by several tissues. Here we review evidence to support this proposition, focussing on experiment performed on glutamine metabolism in immune tissues and white adipose tissue.

Adipose Tissue↗
PubMed1987

Maximum activities of some key enzymes of glycolysis, glutaminolysis, Krebs cycle and fatty acid utilization in bovine pulmonary endothelial cells.

Despite the importance of endothelial cells little is known about their metabolic fuel requirements. To provide some information in this area, the maximum catalytic activities of key enzymes of important metabolic pathways have been measured in bovine pulmonary endothelial cells. The results suggest that both glucose and glutamine are important fuels for these cells: in addition, the oxidation of fatty acids may also be of quantitative significance. The activity of glutaminase in these cells was about 20-fold higher than that in lymphocyte, a cell which exhibits high rates of glutaminolysis. It is suggested that a high rate of glutamine metabolism by endothelial cells is important not only for energy provision but also for provision of nitrogen for biosynthetic purposes including production of local messengers.

Animals↗
PubMed1987

The role of the citric acid cycle in cells of the immune system and its importance in sepsis, trauma and burns.

Many aspects of the cell biology of lymphocytes and macrophages have been studied extensively over many years. Our recent work on these cells has investigated the fuels utilized, the metabolism carried out and the importance of this metabolism for the specific function of these cells in the immune system. The quantitatively important role of glutamine and the observation that both glutamine and glucose are only partially oxidized by both types of cell have been established. This work has led to a new hypothesis to explain the high rates of partial oxidation of both fuels in lymphocytes and macrophages, and in other cells such as enterocytes, colonocytes and also in neoplastic cells. In addition, the high rate of glutamine utilization and its importance in such cells has raised the question as to the source of this glutamine in the body: the evidence suggests that this is muscle. The metabolic relationship between the glutamine-producing tissue and the cells of the immune system provides an explanation for some well-established changes in metabolism during the condition of surgery, trauma, sepsis and burns. Knowledge of the metabolism of glucose, glutamine, pyruvate and long-chain fatty acids by these cells raises some intriguing questions concerning the role and function of the citric acid cycle in these and other similar cells, including tumour cells.

Animals↗
PubMed1986

Metabolism of glucose, glutamine, long-chain fatty acids and ketone bodies by murine macrophages.

Maximum activities of some key enzymes of metabolism were studied in elicited (inflammatory) macrophages of the mouse and lymph-node lymphocytes of the rat. The activity of hexokinase in the macrophage is very high, as high as that in any other major tissue of the body, and higher than that of phosphorylase or 6-phosphofructokinase, suggesting that glucose is a more important fuel than glycogen and that the pentose phosphate pathway is also important in these cells. The latter suggestion is supported by the high activities of both glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. However, the rate of glucose utilization by 'resting' macrophages incubated in vitro is less than the 10% of the activity of 6-phosphofructokinase: this suggests that the rate of glycolysis is increased dramatically during phagocytosis or increased secretory activity. The macrophages possess higher activities of citrate synthase and oxoglutarate dehydrogenase than do lymphocytes, suggesting that the tricarboxylic acid cycle may be important in energy generation in these cells. The activity of 3-oxoacid CoA-transferase is higher in the macrophage, but that of 3-hydroxybutyrate dehydrogenase is very much lower than those in the lymphocytes. The activity of carnitine palmitoyltransferase is higher in macrophages, suggesting that fatty acids as well as acetoacetate could provide acetyl-CoA as substrate for the tricarboxylic acid cycle. No detectable rate of acetoacetate or 3-hydroxybutyrate utilization was observed during incubation of resting macrophages, but that of oleate was 1.0 nmol/h per mg of protein or about 2.2% of the activity of palmitoyltransferase. The activity of glutaminase is about 4-fold higher in macrophages than in lymphocytes, which suggests that the rate of glutamine utilization could be very high. The rate of utilization of glutamine by resting incubated macrophages was similar to that reported for rat lymphocytes, but was considerably lower than the activity of glutaminase.

Animals↗
PubMed1986

Activities of some key enzymes of carbohydrate, ketone body, adenosine and glutamine metabolism in liver, and brown and white adipose tissues of the rat.

In general, the activities of enzymes in brown adipose tissue (BAT) are more similar to those in white adipose tissue than those in liver. Thus the activities of the glycolytic enzymes hexokinase and 6-phosphofructokinase are high but those of glucose 6-phosphatase and fructose bisphosphatase are non-detectable in the two adipose tissues. The activity of HMG-CoA synthase was non-detectable in BAT indicating that this tissue, unlike liver, cannot produce ketone bodies from fatty acid oxidation but, since the tissue possesses a high activity of HMG-CoA lyase, it might produce ketone bodies from leucine catabolism. The findings suggest that 'metabolically' brown adipose tissue can be classified better as an adipose tissue than as a peripheral liver. A high activity of 3-oxoacid CoA transferase but a non-detectable activity of 3-hydroxybutyrate dehydrogenase suggests that BAT can utilise acetoacetate but not 3-hydroxybutyrate for heat generation during cold exposure plus starvation.

Adenosine↗
PubMed1986

Intracellular distribution of some enzymes of the glutamine utilisation pathway in rat lymphocytes.

In lymphocytes of the rat, pyruvate kinase, phosphoenolpyruvate carboxykinase and NADP+-linked malate dehydrogenase (decarboxylating) are distributed almost exclusively in the cytosol whereas pyruvate carboxylase is distributed almost entirely in the mitochondria. For NAD+-linked malate dehydrogenase and aspartate aminotransferase approximately 80% and 40%, respectively, are in the cytosolic compartment. Since glutaminase is present in the mitochondria, glutamine is converted to malate within the mitochondria but further metabolism of the malate is likely to occur in the cytosol. Hence pyruvate produced from this malate, via oxaloacetate and phosphoenolpyruvate carboxykinase, may be rapidly converted to lactate, so restricting the entry of pyruvate into the mitochondria and explaining why very little glutamine is completely oxidised in these cells despite a high capacity of the Krebs cycle.

Animals↗
PubMed1986

Metabolic changes of twenty weeks food-restriction schedule in rats.

In previous studies several metabolic and hormonal adaptations were detected as a consequence of food restriction schedule (single daily meal offered during two hours from 7:30 to 9:30 a.m.) imposed for four weeks. During this period, the most prominent metabolic adaptations were: high alimentary efficiency, delayed gastric emptying, high hepatic glycogen concentration during the intermeal periods, glycemic maintenance during 22 hours of intermedal period as were low mobilization of free fatty acids. In the present work these metabolic adaptations were studied for twenty weeks. The results obtained show that the metabolic and hormonal pattern, defined during four weeks of training to such alimentary scheme, was maintained even after the 20th week. Moreover, it was clear that neither did the body weight increase rapidly nor did it reach that of free-fed rats, after adaptation phase, as reported by other authors.

Adaptation, Physiological↗
PubMed1986

Effect of Stevia rebaudiana on glucose tolerance in normal adult humans.

The effect of aqueous extracts of Stevia rebaudiana leaves on a glucose tolerance test was investigated in 16 normal volunteers. Aqueous extracts of 5 grams of leaves were administered to volunteers at regular 6-h intervals for 3 days. Glucose tolerance tests were performed before and after extract administration. A second group of 6 normal volunteers who ingested an aqueous arabinose solution was also studied to eliminate possible stress effects. The extract of Stevia rebaudiana increased glucose tolerance. The extract significantly decreased plasma glucose levels during the test and after overnight fasting in all volunteers.

Adult↗
PubMed1984

Metabolic performance of free fed rats subjected to prolonged fast as compared to the metabolic pattern in rats under long term food restriction.

Glycemia, free fatty acids, insulinemia, hepatic glycogen, adrenal ascorbic acid, the amount of food ingested and of feces eliminated, gastric emptying and body weight were measured in two groups of rats of the same age. The F, free fed group was subjected to fast during 22 hours and then had a final meal for two hours. The R rats, subjected to food restriction from one to four weeks, had also a final two hour meal after the regular period of 22 hours with no access to food, and then both groups were treated equally. Coincidently, gastric emptying was more delayed, liver glycogen concentration was highest and glycemia was better maintained in the R than the F rats, particularly after three and four weeks of training. Probably due to their greater dependence upon the more frequent supply of nutrients, the F group had a larger free fatty acids mobilization during fast. Adrenal hyperactivity was induced in both groups and the amount of food ingested progressively increased in the R group and decreased in the F group. In general the metabolic efficiency tended to converge to a similar order of magnitude in both groups of animals by the end of the third week. A delayed gastric emptying seems to be a major factor in the adaptations to food restriction.

Adrenal Glands↗