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Biomedical subjects

R Curi

Publications and source records attributed to R Curi.

At least 163 records · Page 9Linked to original sources
PubMed1993

Effects of glucocorticoids on lymphocyte metabolism.

The immunosuppressive effect of glucocorticoids has been widely reported; however, the mechanism of action of these hormones on the immune system has not been fully established. In the present study, the effect of glucocorticoids on glucose, glutamine, and pyruvate metabolism in lymph node lymphocytes was investigated. Addition of dexamethasone to the incubation medium did not alter glucose and glutamine metabolism but inhibited pyruvate utilization by 40%. This latter effect took 1 h to occur and remained for up to 6 h, even after removal of dexamethasone from the culture medium. Measurements of the activity of pyruvate dehydrogenase in lymphocytes and the rate of [1-14C]-pyruvate conversion into 14CO2 in incubated lymphocyte mitochondria demonstrated that glucocorticoids decrease pyruvate utilization by inhibiting the activity of this key regulatory enzyme. The effect of such an inhibition of pyruvate utilization on the function of cells of the immune system remains to be clarified.

Animals↗
PubMed1993

Effect of a polyunsaturated fatty acid-rich diet on macrophage and lymphocyte metabolism of diabetic rats.

Diabetic subjects present high susceptibility to infections but the mechanisms involved are not fully known. Macrophages and lymphocytes utilize glucose and glutamine at high rates and these metabolites are important for the function of these cells. The present study examines the activities of key metabolic enzymes in macrophages and lymphocytes obtained from alloxan-diabetic Wistar rats (10 weeks old, 7 rats each group). Since the enteral diet was enriched with omega-6 polyunsaturated fatty acids (PUFA), the effect of these fatty acids was also investigated in the same animals. Diabetes caused a marked decrease of hexokinase activity (48%; 274.23 +/- 18.43 vs 143.29 +/- 10.35 units for control vs diabetic rats) in macrophages and of citrate synthase and glucose-6-phosphate dehydrogenase activities (70%; 321.76 +/- 9.18 vs 96.25 +/- 5.43 units for citrate synthase and 89.43 +/- 2.33 vs 23.13 +/- 1.09 units for G6PDh for control vs diabetic rats) in mesenteric lymph node lymphocytes. A PUFA-rich diet given for 6 weeks enhanced hexokinase activities by 30% (274.23 +/- 18.43 vs 342.48 +/- 15.39, balanced vs PUFA-rich diets for normal and 143.29 +/- 10.35 vs 189.67 +/- 9.57 for diabetic rats) and reduced citrate synthase activities by 43% (30.31 +/- 1.73 vs 17.42 +/- 0.95, balanced vs PUFA-rich diets for normal and 29.34 +/- 1.23 vs 16.73 +/- 1.02 for diabetic rats) in macrophages, and reduced (< 50%; 59.67 +/- 3.45 vs 48.87 +/- 3.37 for hexokinase and 321.76 +/- 2.33 vs 161.66 +/- 9.97 for citrate synthase, balanced vs PUFA-rich diets) the activities of both enzymes in lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Alloxan↗
PubMed1993

Pyruvate is a lipid precursor for rat lymphocytes in culture: evidence for a lipid exporting capacity.

Since acetyl-CoA produced through pyruvate dehydrogenase reaction is poorly oxidized by the Krebs cycle in rat lymphocytes, the fate of acetyl units was investigated in these cells. The results presented here show that 24-h cultured lymphocytes actively synthesize lipids from [3-14C]pyruvate. Furthermore, a considerable amount of these lipids have shown to be exported into the culture medium. Experiments with [1-14C] acetate as a lipid precursor showed a close similarity with the rates of incorporation of [3-14C] pyruvate into the same lipid fractions. Treatment of lymphocytes with the mitogen concanavalin A (Con A) markedly enhanced [1-14C] acetate incorporation into a variety of lipids, but the lectin did not affect [3-14C] pyruvate incorporation. The results suggest that lymphocytes convert pyruvate into lipids via the acetyl-CoA pathway and that Con A interferes in lymphocyte lipogenesis but does not seem to affect the pyruvate dehydrogenase reaction. The ability to incorporate pyruvate into certain lipids may have an important role for the rapidly dividing capacity of lymphocytes since the human cancer strain HeLa 155 (a quickly proliferating cell line) also exhibits this feature by converting much more [3-14C] pyruvate into lipids than do lymphocytes. In addition, comparative experiments with lymphocytes, peritoneal macrophages and HeLa cells indicate that pyruvate may provide precursors for cells with active lipid producing and exporting capacities.

Acetates↗
PubMed1993

Effects of various dietary fatty acids on enzyme activities of carbohydrate and glutamine metabolism and the metabolic response of lymphocytes and macrophages during Walker-256 ascites cell tumour growth in rats.

It was previously shown that polyunsaturated and saturated fatty acid rich diets affected metabolic and functional changes in macrophages and a variety of immune tissues (thymus, mesenteric lymph nodes and spleen). This study reports metabolic and functional changes in peritoneal macrophages and lymphocytes of Walker-256 ascites cell tumour-bearing rats which were fed (a) normal balanced diet (3% fat), (b) diet enriched (15% fat) with polyunsaturated fatty acids or (c) diet fortified (15% fat) with saturated fatty acids. Neither of the fatty acid enriched diets affected macrophage migration following tumour cell implantation and ascitic cell growth. However both of these fortified fatty acid regimes enhanced the production of H2O2 by macrophages and lymphocytes. The maximum catalytic capacities of hexokinase, glutaminase, glucose-6-phosphate dehydrogenase and glutathione peroxidase were measured in resident and tumour activated macrophages and lymphocytes obtained from rats fed the three fatty acid dietary regimes during seven days of tumour ascites cell growth. Tumour growth caused an increase in the activities of all of the above enzymes in macrophages irrespective of the fatty acid composition of the diet and notably decreased, independent of dietary fatty acid composition, the activities of the enzymes in lymphocytes. Only glutaminase activity in the lymphocytes of tumour bearing animals fed an unsaturated fatty acid-rich diet was not reduced, but was increased by 78%. Moreover macrophages from control rats fed an enriched polyunsaturated fatty acid diet had increased hexokinase activity (21%), decreased glutaminase (48%) and citrate synthase (decreased 41%) relative to the activities of these enzymes in macrophages of animals maintained on a balanced fatty acid diet. The feeding of both fatty acid rich diets did not modify the pattern of lymphocyte responses during the growth of tumour cells in these animals. None of the fatty acid diets modified the growth rate nor the yield of tumour cells in the peritoneal cavity.

Animals↗
PubMed1992

Effect of epinephrine on glucose metabolism and hydrogen peroxide content in incubated rat macrophages.

The effects of epinephrine on glucose metabolism and hydrogen peroxide content were examined in incubated rat macrophages. An increase in the activities of hexokinase and citrate synthase and a reduction in that of glucose-6-phosphate dehydrogenase was found in resident, inflammatory and activated macrophages incubated for 1 hr in the presence of epinephrine. Glucose utilization by incubated resident, inflammatory and activated macrophages was augmented markedly by the addition of epinephrine, whereas lactate formation was depressed. Under the same conditions, there was a 2.6-fold increment of hydrogen peroxide content and of [U-14C]glucose decarboxylation in activated macrophages incubated for 40 min. Similar results were obtained when pyruvate and oxoglutarate was substituted for glucose. These findings suggest that epinephrine may increase hydrogen peroxide production in activated macrophages possibly through a mitochondrial mechanism other than the pentose-phosphate pathway. Between 40 and 90 min of incubation, the content of hydrogen peroxide decreased markedly, and there was no detectable glucose utilization in the presence of epinephrine. These observations are consistent with the idea that this catecholamine stimulates both hydrogen peroxide production and metabolism, the first process being dependent on mitochondrial fuels.

Animals↗
PubMed1992

Metabolic mechanisms involved in the impaired insulin secretion in pancreatic islets isolated from exercised and fasted rats.

This study examined the metabolic mechanisms involved in the impaired insulin secretion by pancreatic islets isolated from fasted and exercised rats. Insulin secretion to glucose (8.3 to 16.7 mM) stimulus was lower in fasted (F), exercised (E), and fasted plus exercised (EF) rats as compared with the control group. The rate of glucose oxidation by isolated islets was reduced in F and EF rats, but it was not modified in the E group. In response to alpha-KIC (5, 10, 15, and 20 mM), insulin secretion was not different in EF and F rats, in comparison to controls, except in the E group, which showed values slightly higher. These findings suggest that changes in insulin secretion in fasted rats, associated or not to exercise training, might be a consequence of a reduced activity of the right-hand side of the Krebs cycle (from pyruvate to oxoglutarate), leading to decreased glucose oxidation. However, the exercise itself caused a significant decrease of insulin secretion without altering glycolysis and Krebs cycle activities.

Animals↗
PubMed1992

Long-term regulation of pancreatic B-cell responsiveness to D-glucose by food availability, feeding schedule, and diet composition.

The immediate metabolic, cationic, and secretory response of the insulin-producing B-cell to D-glucose is regulated, in a delayed or long-term manner, by nutritional factors such as food availability, feeding schedule, or diet composition. The B-cell keeps the memory of these nutritional manipulations so that the corresponding changes in its responsiveness to D-glucose can be documented in vitro in isolated pancreatic islets. The results of experiments conducted in starved rats, in animals exposed to an altered feeding schedule, and in rats given free access to a high-carbohydrate, high-protein, or high-lipid, as distinct from balanced, diet all suggest that a sufficient prandial hyperglycemia is essential for maintenance of an optimal metabolic and secretory behavior of the islet B-cell in response to a rise in D-glucose concentration.

Animals↗
PubMed1992

Utilization of rat and human sera to carry out incubation and perifusion of pancreatic islets.

Incubation of isolated pancreatic rat islets in a medium consisting of fresh rat or human sera and the measurement of insulin secretion after 60 min in the presence of 6.0-7.0 and 16.7 mM of glucose, were carried out. Perifusion experiments with isolated rat islets preincubated in the presence of rat or human sera and 0.2 mCi/mL of 45Ca2+ were also performed, and 45Ca2+ outflow rate and insulin secretion were analyzed. In both experiments, the usual islet responsiveness to glucose stimulation was preserved when compared with experiments in which Krebs-Henseleit (K-H) buffer was used as the medium. The results obtained demonstrate that both rat and human sera can be used as media for islets perifusion and incubation experiments, thus allowing for the effect(s) of circulating substances on insulin release to be examined.

Adult↗
PubMed1992

5-aminolevulinic acid-induced alterations of oxidative metabolism in sedentary and exercise-trained rats.

5-Aminolevulinic acid (ALA), a heme precursor that accumulates in acute intermittent porphyria patients and lead-exposed individuals, has previously been shown to autoxidize with generation of reactive oxygen species and to cause in vitro oxidative damage to rat liver mitochondria. We now demonstrate that chronically ALA-treated rats (40 mg/kg body wt every 2 days for 15 days) exhibit decreased mitochondrial enzymatic activities (superoxide dismutase, citrate synthase) in liver and soleus (type I, red) and gastrocnemius (type IIb, white) muscle fibers. Previous adaptation of rats to endurance exercise, indicated by augmented (cytosolic) CuZn-superoxide dismutase (SOD) and (mitochondrial) Mn-SOD activities in several organs, does not protect the animals against liver and soleus mitochondrial damage promoted by intraperitoneal injections of ALA. This is suggested by loss of citrate synthase and Mn-SOD activities and elevation of serum lactate levels, concomitant to decreased glycogen content in soleus and the red portion of gastrocnemius (type IIa) fibers of both sedentary and swimming-trained ALA-treated rats. In parallel, the type IIb gastrocnemius fibers, which are known to obtain energy mainly by glycolysis, do not undergo these biochemical changes. Consistently, ALA-treated rats under swimming training reach fatigue significantly earlier than the control group. These results indicate that ALA may be an important prooxidant in vivo.

Aminolevulinic Acid↗
PubMed1992

Effects of insulin, glucocorticoids and thyroid hormones on the activities of key enzymes of glycolysis, glutaminolysis, the pentose-phosphate pathway and the Krebs cycle in rat macrophages.

In the present study the effects of insulin, glucocorticoids and thyroid hormones on macrophage metabolism and function were investigated. The maximum activities of hexokinase, glucose-6-phosphate dehydrogenase, glutaminase and citrate synthase were determined in macrophages obtained from hormone-treated rats and those cultured for a period of 48 h in the presence of hormones. Macrophage phagocytosis was markedly inhibited by dexamethasone and thyroid hormones, remaining unchanged when insulin was added to the culture medium, however. The changes in the enzyme activities caused by hormone treatments of the rats were very similar to those found in culture. Insulin enhanced citrate synthase and hexokinase activities and diminished those of glutaminase and glucose-6-phosphate dehydrogenase. Dexamethasone had a similar effect except on glucose-6-phosphate dehydrogenase. The addition of thyroid hormones to the culture medium raised the activities of glutaminase and hexokinase and reduced that of citrate synthase. The results presented support the suggestion that the effects of insulin, glucocorticoids and thyroid hormones on immune and inflammatory responses could well be mediated through changes in macrophage metabolism.

Animals↗
PubMed1992

Effect of aging on the glutaminase activity of neoplastic and immune tissues.

1. The effect of age and Walker 256 tumor on maximal phosphate-dependent glutaminase activity of rat immune tissue was determined. Glutaminase is a key enzyme in the metabolism of glutamine, an important fuel for normal and neoplastic cells. 2. Maximal activity of phosphate-dependent glutaminase was measured in immune tissues and tumors of Walker 256 tumor-bearing young (28 days old), mature (3 months old) and aged (15 months old) Wistar rats. The following tissues were examined: thymus, spleen, mesenteric lymph nodes and tumor. 3. Tumor implantation for 14 days reduced glutaminase activity in the thymus and mesenteric lymph nodes. Tumor glutaminase activity was lowest in aged rats and highest in the mature group. 4. Comparison of glutaminase activity in immune and tumor tissues suggested the flux of glutamine between these tissues in the 3 groups. Glutaminase activity was 2.8-fold higher in immune tissues in aged rats (2.58 +/- 0.35 vs 0.93 +/- 0.16 mumol min-1 g tissue wet weight-1, mean +/- SEM, 5 rats), and 1.9- (4.14 +/- 0.47 vs 8.36 +/- 1.29 mumol min-1 g tissue wet weight-1, mean +/- SEM, 5 rats) and 2.5-fold increased (2.41 +/- 0.20 vs 5.92 +/- 0.22 mumol min-1 g tissue wet weight-1, mean +/- SEM, 5 rats) in tumor tissue in the mature and young groups, respectively. These results suggest the deviation of glutamine flux from defense cells to the neoplastic tissue in tumor-bearing young and mature rats and may partially explain the slow cancer growth in elderly patients.

Aging↗
PubMed1992

In vivo effect of glucocorticoids on the rates of pyruvate utilization and lactate formation by incubated lymphocytes.

Although the immunosuppressive effect of glucocorticoids has been widely reported, the mechanism of action of these hormones on the immune system has not been fully established. In the present study, the effect of glucocorticoids on the rates of pyruvate utilization and lactate production by lymphocytes obtained from rat mesenteric lymph nodes was investigated. Adult rats were injected with dexamethasone (1 mg/kg, ip) daily for 3 days. A stressed group which received a corresponding volume of 0.9% saline and control rats not injected were also included. All treatments were carried out at 17:00 h. Stress or administration of dexamethasone reduced the rate of pyruvate utilization by 50% and 62%, respectively. The hormonal injection increased the rate of lactate production by 57%, whereas the stressed group showed a 2.4-fold increase of the conversion of pyruvate to lactate, as compared to control rats. These findings suggest that glucocorticoids regulate pyruvate metabolism in lymphocytes and that an additional neurohormonal factor released during stress may also participate in the control of lactate production.

Animals↗
PubMed1992

Possible role of the submandibular glands in the control of glucose metabolism in mouse enterocytes.

We evaluated the effect of sialadenectomy on hexokinase activity and on rates of lactate formation and of [U-14C]glucose decarboxylation in 3 cellular fractions of the small intestine epithelium from male adult mice. The surgery was carried out under ether anesthesia and a sham-operated group was used as control. Three cell fractions were obtained by shaking the inverted small intestine: 1) tip of the villus, 2) villus and 3) villus and crypt cells. Five days after sialadenectomy, hexokinase activity was reduced in fractions 1 (3.53 +/- 0.65 vs 1.98 +/- 0.25 nmol min-1 mg protein-1, expressed as mean +/- SEM for 7 mice) and 3 (5.01 +/- 0.55 vs 3.15 +/- 0.42 nmol min-1 mg protein-1, mean +/- SEM for 7 mice). After removal of the submandibular glands, the rates of lactate formation were decreased in fractions 2 (4.16 +/- 0.54 vs 2.30 +/- 0.25, mean +/- SEM for 10 and 11 mice, respectively) and 3 (1.74 +/- 0.24 vs 0.87 +/- 0.14, mean +/- SEM for 13 mice) and the rates of [U-14C] glucose decarboxylation were reduced in fraction 1 (1.14 +/- 0.12 vs 0.61 +/- 0.10, mean +/- SEM for 11 and 12 mice, respectively). We conclude that the secretion of submandibular glands plays a physiological role in the control of glucose metabolism in enterocytes.

Animals↗
PubMed1992

Metabolic and functional changes in macrophages of rats fed polyunsaturated or saturated fatty acid rich-diets during ageing.

Previous reports from our laboratory showed that rats fed a polyunsaturated fatty acid-rich diet (UC), during an acute intervals, present important changes in macrophage metabolism and function, while a saturated fatty acid diet (SC) did not induce significant changes (10). In this study, two important questions were addressed: 1. the persistence of the changes induced by the UC and 2. the effect of a SC offered during ageing. The maximal activities of hexokinase, glucose-6-phosphate dehydrogenase, glutaminase, citrate synthase and glutathione peroxidase and the total content of lipid peroxides were measured in resident and inflammatory macrophages of rats fed control chow (CC), UC or SC during 14 months. Intraperitoneal cell migration by thioglycollate injection and the phagocytosis capacity were also evaluated. The results indicate that: 1) the changes caused by UC are exacerbated during ageing, and 2) the SC, given during a prolonged period of time, also caused important alterations of macrophage metabolism and function.

Administration, Oral↗
PubMed1991

The effect of tumour bearing on skeletal muscle glutamine metabolism.

1. The effects of tumour bearing on glutamine metabolism in rat skeletal muscle were examined using the Walker 256 carcinosarcoma. 2. There was a rapid and marked decrease in skeletal muscle glutamine content, which was correlated with the size of the tumour, and a decrease in plasma glutamine concentration. 3. The rate of release of glutamine from EDL muscle in vitro was increased in cachectic, tumour bearing animals, but was unaffected from the soleus muscle of the same animals. 4. It is hypothesized that the increase in the rate of muscle glutamine release during cachexia represents a response of this tissue in order to satisfy the demand for glutamine by the tumour or by cells of the immune system.

Animals↗
PubMed1991

Insulin secretion to glucose stimulus in pancreatic islets isolated from rats fed unbalanced diets.

To verify the effect of different energetic sources on insulin secretion, just-weaned male Wistar rats were divided into four groups fed as follows: high carbohydrate (HC), high protein (HP), high lipid (HL) and balanced (C) diets during five weeks. Body weight gain and daily food intake were similar among the four groups. Insulin content of the isolated islets was not different; however, insulin release to a high glucose concentration (16.7 mM) stimulus was clearly higher in islets isolated from rats fed a balanced diet as compared to the other groups (HC, HP and HL). The rates of insulin secretion in islet perfusates from rats fed unbalanced diets were also decreased, although 45Ca2+ outflow rate (FOR) was similar in all groups. Since the rate of U-14C-glucose oxidation was decreased in islets isolated from rats fed unbalanced diets, this could be one of the mechanisms for the reduced rates of insulin release observed. Therefore, the increased supply of specific fuels provoke metabolic alterations in B-cell leading to changes in insulin secretion.

Animals↗
PubMed1991

Metabolic changes of several adipose depots as caused by aging.

In this study, metabolic changes of several adipose depots as caused by aging were investigated. Key enzyme activity of glutaminolysis, pentose-phosphate pathway and Krebs cycle were measured. The rates of lipogenesis from 3H2O, lipoprotein lipase (LPL) activity and rate of lipolysis in vitro were also determined. The results obtained indicate a reduced capacity for lipogenesis in several adipose depots by aging. The authors concluded that hypertrophy of adipose tissue reported during aging is possible due to increased LPL activity and reduced rate of lipolysis.

Adipose Tissue↗