Biomedical subjects

R Curi

Publications and source records attributed to R Curi.

At least 127 records · Page 7Linked to original sources

PubMed1996

Modulation of insulin secretion by feeding behavior and physical activity: possible beneficial effects on obese and aged rats.

The high occurrence of diabetes in aged subjects is well known. In fact, the aging process is accompanied by obesity and presenting increased insulin release and lower peripheral responsiveness to this hormone. A recent study has shown that the changes in glucose utilization and insulin secretion during aging are abolished when obesity is somehow avoided. This fact justifies the effort to define new strategies to avoid the development of obesity during aging. In this review, beneficial effects of balanced diets, high frequency food intake and moderate exercise training on insulin secretion and its effect in rats are presented.

Aging↗

PubMed1996

Administration of fish oil by gavage increases the activities of hexokinase, glucose-6-phosphate dehydrogenase, and citrate synthase in rat lymphoid organs.

1. The effect of administration of fish oil by gavage on key enzyme activities of glucose metabolism of the thymus, spleen, and mesenteric lymph nodes was investigated. 2. The activities of hexokinase, glucose-6-phosphate dehydrogenase, and citrate synthase in the lymphoid organs were markedly raised due to a daily administration of fish oil by gavage (0.4% of body weight). 3. These findings indicate that the therapeutic utilization of fish oil does affect the metabolism of the lymphoid organs, and possibly immune function; however, the mechanism involved remains to be investigated.

Animals↗

PubMed1996

Studies on the lipid metabolism of Walker 256 tumour-bearing rats during the development of cancer cachexia.

Aspects of the lipid metabolism of Walker 256 carcinosarcoma-bearing cachectic rats (TB) were investigated during a 14 day interval of tumour growth. Food intake and body weight of the TB rats were reduced by 18% and 13%, respectively, on day 14, as compared with non-tumour-bearing animals. The tumour burden then, corresponded to 19% of total body weight. The total fat content was not different in the liver, heart, carcass, epididymal (EAT) and retroperitoneal (RPAT) adipose tissues of the two groups. The brown adipose tissue (BAT) and skeletal muscle (gastrocnemius-SM) of the TB rats had increased levels of fat (23% and 200%, respectively). Enteral absorption of 14C-triolein was decreased in the TB rats, but the liver, heart, and SM of these animals incorporated more radiolabelled lipid than the control animals, while the adipose tissues exhibited a decreased incorporation of radioactivity in relation to controls. More lipid was incorporated into the VLDL fraction secreted by the liver of TB rats, which exhibited a different distribution of the incorporated 14C-oleate in the various lipid subfractions. Ultrastructural studies showed that the hepatocytes of the TB rats had a greater incidence of lipid droplets in the cytoplasm.

Adipose Tissue↗

PubMed1996

Impairment of insulin secretion in pancreatic islets isolated from Walker 256 tumor-bearing rats.

Previous study has shown that insulin secretion in response to a glucose stimulus (16.7 mM) is reduced in islets isolated from Walker 256 tumor-bearing rats compared with controls. The ultrastructure, 45Ca2+ and 86Rb+ fractional outflow rate, phosphoinositide hydrolysis, and [U-14C]glucose decarboxylation were examined in islets isolated from tumor-bearing and control rats. The general morphological features of the islets from the control and experimental groups were very similar. The 86Rb+ fractional outflow rate was not changed, whereas the 45Ca2+ fractional outflow rate, [U-14C]glucose decarboxylation, and phosphoinositide metabolism were markedly reduced in islets from tumor-bearing rats. The changes in 45Ca2+ fractional outflow rate in islets from tumor-bearing rats were not due to impaired functioning of voltage-dependent calcium channels. By perifusing the islets in the presence of high potassium concentration, evidence was obtained that phospholipase C from islets from tumor-bearing rats reduced response to calcium. To further examine the mechanism involved in the impairment of insulin secretion by islets from tumor-bearing rats, islets isolated from normal rats were perifused after preincubation in the presence of serum from tumor-bearing rats. The results suggest that a thermolabile circulating factor is partially responsible for the changes described in islets isolated from Walker 256 tumor-bearing rats.

Animals↗

PubMed1996

Fatty acid oxidation in lymphocytes from Walker 256 tumor-bearing rats.

The oxidation of fatty acids in lymphocytes from the mesenteric lymph nodes of Walker 256 carcinosarcoma-bearing rats (TB) was studied, as well as the activity of the mitochondrial long-chain fatty acid transport system. Two-month old Wistar rats were subcutaneously implanted with 10(7) cells and after 2 weeks the tumor mass was 15-20% of the carcass weight. The activity of carnitine palmitoyltransferase (CPT) II was demonstrable in the lymphocytes of the TB group (8.2 +/- 5.6 nmol/min per mg mitochondria protein for 15 rats) and was not detected in the control, while that of CPT I was only slightly increased in the former. Similar rates of [1-14C]-palmitate decarboxylation were found for TB and control rat lymphocytes. However, when the rate of decarboxylation of [1-14C]-palmitate present in the intracellular pool of lipids was investigated in cultured lymphocytes, the cells of TB rats exhibited rates 17-fold higher than those of control animals in the presence of fetal calf serum (FCS). Decarboxylation in the presence of TB rat serum was 178-fold higher than obtained with normal rat serum, and 1.4-fold compared to FCS. These results suggest that, during cachexia, lymphocytes preferably oxidize intracellular lipids, and that this capacity is greatly enhanced by factors circulating in the serum of tumor-bearing rats.

Animals↗

PubMed1996

Immunodetection of rat Walker 256 tumour mitochondrial carnitine palmitoyltransferase I and II: evidence for the control of CPT II expression by insulin.

The purpose of the study was to separate the mitochondrial proteins of rat Walker 256 tumour tissue and perform immunodetection studies to identify the carnitine palmitoyltransferase I (CPT I) and CPT II proteins previously reported to be present in this tumour. CPT I protein was undetectable using antibody raised against rat liver CPT I and was therefore considered to be immunologically different from that found in normal rat tissues such as heart, liver and skeletal muscle. In contrast, CPT II protein was readily detected in Walker 256 tumour and had an apparent Mr of approximately 70,000, as was found for rat liver. The in vivo treatment of tumour-bearing rats with insulin caused an increase in the expression of CPT II protein in the tumour tissue. The data confirm that CPT II can be regulated by insulin and also demonstrate that tumour CPT I may be a different isoform from that present in rat liver.

Animals↗

PubMed1996

Possible modulatory role of non-activated lymphocytes on insulin secretion.

In order to study the probable physiological role of non-activated lymphocytes on islet B-cells, we incubated and perfused rat pancreatic islets in the presence of low (2.8 mM) and high (16.7 mM) glucose concentrations after pre-exposure for 60 min to rat lymphocytes or to substances secreted by lymphocytes. Insulin secretion and 86Rb+, 45Ca2+ and [3H]-phosphoinositide metabolite fluxes were lower compared to controls when islets were pre-exposed to lymphocytes but were not different when islets were pre-exposed to substances secreted by lymphocytes. These alterations in isotope flux suggest that, when lymphocytes and islets are in contact, closure of potassium channels and a paradoxical effect of glucose load on insulin release occur in the presence of low glucose concentrations. The alterations observed are probably due to a swift and direct action of lymphocyte secretion perhaps induced by a direct of islet cells.

Animals↗

PubMed1995

Hormonal regulation of superoxide dismutase, catalase, and glutathione peroxidase activities in rat macrophages.

This study examined the effects of glycocorticoids, insulin, thyroxine, and epinephrine upon the activities of CuZn- and Mn-superoxide dismutases (SOD), catalase, and glutathione peroxidase (GPX) and upon hydrogen peroxide production in rat macrophages obtained from the intraperitoneal cavity. The experiments were performed in vivo under conditions causing hormonal dysfunctions: adrenal demedullation, dexamethasone treatment, thyroidectomy, administration of L-tri-iodothyronine (T3) and L-thyroxine (T4), and diabetes. Macrophages were also cultured for 24 hr in the presence of dexamethasone, thyroid hormones, and insulin as to evaluate possible interferences caused in vivo by changes in other hormones. The results indicated that these hormones do control the activities of the antioxidant enzymes and hydrogen peroxide production both in vivo and in vitro. Insulin increased the activities of CuZn-SOD, catalase, and GPX and reduced that of Mn-SOD. Thyroid hormones raised the activities of CuZn- and Mn-SOD and decreased that of GPX, whereas glucocorticoids reduced both Mn-SOD and GPX. The removal of the adrenal medulla caused a decrease of Mn-SOD and GPX activities in the macrophages. Hydrogen peroxide production was increased by insulin and reduced by thyroid hormones and glucocorticoids. The changes in antioxidant enzyme activities caused by these hormones in macrophages may indicate important mechanisms for the establishment of impaired immune function in endocrine pathologies.

Animals↗

PubMed1995

Effect of adrenaline and phorbol myristate acetate or bacterial lipopolysaccharide on stimulation of pathways of macrophage glucose, glutamine and O2 metabolism. Evidence for cyclic AMP-dependent protein kinase mediated inhibition of glucose-6-phosphate dehydrogenase and activation of NADP+-dependent 'malic' enzyme.

Adrenaline has recently been shown to stimulate both glucose metabolism and H2O2 release by macrophages but the activity of the key pentose phosphate pathway enzyme, glucose-6-phosphate dehydrogenase (which generates the NADPH crucial for the reduction of molecular oxygen), was reduced under these conditions [Costa Rosa, Safi, Cury and Curi (1992) Biochem. Pharmacol. 44, 2235-2241]. We report here that adrenaline activates another NADPH-producing enzyme, NADP(+)-dependent 'malic' enzyme, while also inhibiting glucose-6-phosphate dehydrogenase, via cyclic AMP-dependent protein kinase (PKA) activation. Regulation of glucose-6-phosphate dehydrogenase activity by PKA has not been reported elsewhere. The sparing of some glucose from pentose phosphate pathway consumption may be important in the provision of glycerol 3-phosphate which in the macrophage may be required for new phospholipid synthesis. Glutamine oxidation was also stimulated by adrenaline thus providing increased substrate (malate) for NADP(+)-dependent 'malic' enzyme and therefore shifting some of the burden of NADPH production from glucose to glutamine metabolism. We also report a novel synergistic effect of adrenaline and some bacterial products and/or gamma-interferon in stimulating secretory and metabolic pathways in macrophages which may be a part of a larger network of signals that lead to enhanced macrophage activity.

Animals↗

PubMed1995

Effect of hypo- and hyperthyroidism on the function and metabolism of macrophages in rats.

The effect of thyroid hormones on monocyte migration, phagocytic capacity and hydrogen peroxide production by macrophages and the effect of these hormones on glutamine and glucose metabolism was investigated. The experiments were performed on resident, thioglycollate- and BCG-stimulated cells from hypo- and hyperthyroid rats. High plasma levels of thyroid hormones suppressed the migration of monocytes and hydrogen peroxide production, whereas hypothyroidism did not affect cell migration but raised the phagocytic capacity and the hydrogen peroxide production. Hyperthyroidism increased the activities of glutaminase and hexokinase and the rates of decarboxylation of [U-14C]-glutamine and [U-14C]-glucose in inflammatory and activated cells. Hypothyroidism stimulated glucose metabolism and had only a slight effect on glutaminolysis. The activity of the TCA cycle was, however, diminished in the presence of high plasma levels of thyroid hormones and enhanced by the hypothyroid state. These findings suggest that the functional changes are more likely to be related to the activity of the TCA cycle rather than to glutaminolysis and glycolysis.

Animals↗

PubMed1995

Effects of feeding lipids of different fatty acid compositions upon rat lymphocyte proliferation.

Weanling Wistar rats were fed for 8 weeks on a low fat (3% by weight) diet (LF) or on diets containing 15% by weight hydrogenated coconut oil (coconut oil), cocoa butter, cashew kernel oil (cashew oil), canola oil or soya bean oil (soya oil). Each of the high fat diets resulted in inhibition of spleen lymphocyte proliferation in response to concanavalin A (Con A), a T-cell mitogen. Feeding the soya oil diet caused more than 95% inhibition of proliferation, compared with feeding the LF diet. Amongst the high fat diets, feeding the cashew, canola or soya oil diets resulted in inhibition of proliferation compared with feeding the coconut oil diet while feeding the soya oil diet resulted in inhibition of proliferation compared with feeding the cocoa butter or canola oil diets. Proliferation of lymphocytes in response to Con A was also investigated using whole blood culture. Once again, feeding the soya oil diet resulted in a dramatic decrease in proliferation (80%) compared with feeding the LF diet. Feeding the soya oil diet also inhibited proliferation compared with feeding the coconut oil, cocoa butter or cashew oil diets. Feeding the canola oil diet resulted in inhibition of proliferation compared with feeding the LF or cocoa butter diets.

Animals↗

PubMed1995

Effect of aspartate, asparagine, and carnitine supplementation in the diet on metabolism of skeletal muscle during a moderate exercise.

The present study examined the effect of diet supplementation of oxaloacetate precursors (aspartate and asparagine) and carnitine on muscle metabolism and exercise endurance. The results suggest that the diet supplementation increased the capacity of the muscle to utilize FFA and spare glycogen. Time to exhaustion was about 40% longer in the experimental group compared to the control, which received commercial diet only. These findings suggest that oxaloacetate may be important to determine the time to exhaustion during a prolonged and moderate exercise.

Animals↗

PubMed1995

Propionate modifies lipid biosynthesis in rat peritoneal macrophages.

1. This study examines the effect of propionate, normally produced in the gut, on lipid metabolism of resident macrophage. This cell is very abundant in the epithelial lining of the gut. 2. The activity of propionyl-CoA synthetase in macrophages was shown to be 0.39 nmol/min per mg protein, so this cell presents the ability to use propionate. Propionate at concentrations varying from 0.5 to 5 mM did not affect the activities of carnitine acetyltransferase, ATP-citrate lyase, acetoacetyl-CoA thiolase and 3-oxoacid-CoA transferase. 3. Thus this short chain fatty acid did not alter the capacity for transferring acetyl-CoA from mitochondria to cytosol and for ketone bodies formation and oxidation. However, propionate (40 mM) inhibited the incorporation of [1-14C]-palmitate into phospholipids, cholesterol, cholesterol ester and triacylglycerol and the incorporation of [3-14C]-pyruvate into phospholipids. 4. These findings suggest that fibre-rich diet by generating propionate may regulate macrophage lipid metabolism.

ATP Citrate (pro-S)-Lyase↗

PubMed1995

Composition of fatty acids in the liver and lymphoid organs of rats fed fatty acid-rich diets.

The composition of the fatty acids in the thymus, spleen and mesenteric lymph nodes was determined in rats fed polyunsaturated (UFC) or saturated (SFC) fatty acid-rich chow during 6 weeks or 14 months. The results indicated that the lipid composition of fatty acids in these tissues was modified by the type of fat given in the diets. Interestingly, the liver did not show any dietary induced change in the composition of fatty acids. The unsaturation index was raised in the lymphoid organs by UFC either after 6 weeks or 14 months. The ageing process itself increased the degree of unsaturation of fatty acids only in the spleen of the 3 groups. A high degree of unsaturation of fatty acids in the tissues may favour the occurrence of lipid peroxidation. It was noteworthy that a linoleic acid-rich diet (UFC) did not change the content of arachidonic acid in the tissues and so would therefore be unlikely to affect eicosanoid synthesis. As shown by previous studies, these fat-rich diets caused marked changes in the key enzyme activities of glucose and glutamine metabolism in the lymphoid organs, by as yet unknown mechanisms. The results reported here suggest that the effect of fat-rich diets on intermediary metabolism does not occur through eicosanoid synthesis and may be a consequence of the lipid peroxidative process or even alterations in the transcription of the enzymes of glycolysis and glutaminolysis.

Aging↗

PubMed1995

Insulin and prostaglandins as signals between tumor and the host immune system.

The development of malignant tissue in vivo is partially favored by the immunosuppression that occurs in cancer patients. However, the signals between tumor and immune tissues remain to be identified. We present evidence that prostaglandins may act as one of these signals by a direct action on cells of the immune system, or by inhibition of insulin secretion which in turn suppresses immune function, or both.

Animals↗

PubMed1995

Human and rat tumour cells possess mitochondrial carnitine palmitoyltransferase I and II: effects of insulin.

In order to investigate the long-chain fatty acid oxidative capacity of tumour cells, carnitine palmitoyltransferase I (CPT I) and CPT II were selected for study because they are rate-limiting regulatory enzymes. Measurable activities of both CPT I and CPT II were detected in several human and rat tumour cell types and in mouse fibroblasts. The activities were comparable with those previously reported for rat liver CPT I and II, ranging from 1-3 nmoles/min/mg protein for both CPT I and II. Walker 256 tumour tissue also contained detectable CPT I and II activities, thereby demonstrating that tumour tissue in vivo also has the capacity for the processing of fatty acyl CoA's in the mitochondrion. The possible regulation of tumour CPT I and II was investigated using the hormone insulin, both in vitro and in vivo. Insulin was found to increase CPT II activity in the T24/83 human bladder tumour in vitro and in the Walker 256 rat tumour in vivo. The results suggest that insulin may exert some control over the activity of CPT II in certain types of tumour. In contrast, insulin was without effect on CPT I activity in any of the tumours studied, either in vitro or in vivo.

Animals↗

PubMed1994

Effect of thioglycollate and BCG stimuli on glucose and glutamine metabolism in rat macrophages.

The macrophage is a differentiated cell that takes part in a wide range of physiological and pathological processes, such as inflammatory and immunological responses. The stimulation of macrophages involves the acquisition of some functional characteristics such as phagocytosis, ability to kill tumor cells, and processing and presentation of antigens. In this study we have investigated the changes in macrophage glucose and glutamine metabolism as induced by stimulation by thioglycollate (inflammatory) and bacille Calmette-Guérin (BCG) (activated). The results showed an increase in hexokinase and citrate synthase activities, due to both stimulatory processes. One difference between inflammatory and activated cells is the higher rate of glucose oxidation in the latter. The activation with BCG, however, also led to an enhancement in glutamine metabolism that is not observed in the inflammatory cell. These results suggest that glutamine metabolism might be important for macrophage function during immunological response.

Animals↗

PubMed1994

Human macrophage metabolism of low density lipoprotein oxidized by stimulated neutrophils and ferritin.

The metabolism of low density lipoprotein (LDL) oxidized with phorbol myristate acetate (PMA) stimulated neutrophils plus ferritin (LDLox) by human monocyte-derived macrophage (HMDM) was studied. Binding of 125I-labeled LDLox to HMDM and further uptake and degradation were higher than for native 125I-labeled LDL. LDLox seems to be taken up by HMDM through the scavenger receptor as indicated by competition studies with unlabeled native and autoxidized LDL. An increased concentration of cellular cholesteryl esters was observed in HMDM exposed to LDLox. Oxidative modification of LDL increased its electrophoretic migration on agarose gel and also the fragmentation of apolipoprotein B. Data suggest that LDLox is incorporated by human macrophages and can potentially induce foam-cell formation.

Binding, Competitive↗