High salt intake during puberty leads to cardiac remodelling and baroreflex impairment in lean and obese male Wistar rats.

Modern lifestyle increases the prevalence of obesity and its co-morbidities in the young population. High-salt (HS) diets are associated with hypertension and cardiac remodelling. The present study evaluated the potential effects of cardiometabolic programming induced by HS intake during puberty in lean and obese rats. Additionally, we investigated whether HS could exacerbate the impairment of cardiovascular parameters in adult life due to postnatal early overnutrition (PO). At postnatal day 3 (PN3), twenty-four litters of Wistar rats were divided into two groups: normal litter (NL, nine pups/dam) and small litter (SL, three pups/dam) throughout the lactation period; weaning was at PN21. At PN30, the pups were subdivided into two more groups: NL plus HS (NLHS) and SL plus HS (SLHS). HS intake was from PN30 until PN60. Cardiovascular parameters were evaluated at PN120. SL rats became overweight at adulthood due to persistent hyperphagia; however, HS exposure during puberty reduced the weight gain and food intake of NLHS and SLHS. Both HS and obesity raised the blood pressure, impaired baro- and chemoreflex sensitivity and induced cardiac remodelling but no worsening was observed in the association of these factors, except a little reduction in the angiotensin type-2 receptor in the hearts from SLHS animals. Our results suggest that the response of newborn offspring to PO and juveniles to a HS diet leads to significant changes in cardiovascular parameters in adult rats. This damage may be accompanied by impairment of both angiotensin signalling and antioxidant defence in the heart.

Characterizing Pharmacogenomic-Guided Medication Use With a Clinical Data Repository.

The extent to which pharmacogenomic-guided medication use has been adopted in various health systems is unclear. To assess the uptake of pharmacogenomic-guided medication use, we determined its frequency across our health system, which does not have a structured testing program. Using a multisite clinical data repository, we identified adult patients' first prescribed medications between January 2011 and December 2013 and investigated the frequency of germline and somatic pharmacogenomic testing, by the Pharmacogenomics Knowledgebase level of the US Food and Drug Administration label information. There were 268,262 medication orders for drugs with germline pharmacogenomic testing information in their drug labels. Pharmacogenomic testing was detected for 1.5% (129/8,718) of medication orders with recommended or required testing. Of the 3,817 medication orders associated with somatic pharmacogenomic testing information in their drug labels, 20% (372/1,819) of required tests were detected. The low rates of detectable pharmacogenomic testing suggest that structured testing programs are required to achieve the success of precision medicine.

Childhood obesity: a (re) programming disease?

The aim of our article was to review the current literature on the effects of metabolic (re) programming on childhood obesity. PubMed/MEDLINE was the data source used to track the studies. Descriptors applied: children obesity, epigenetic, metabolic programming, exercise and nutrition. The focus was to analyze and discuss the international findings on the theme. The gathering of the papers was performed between June and August 2014. The search of articles with the descriptors used found 33.054 studies. In all, 5.709 studies were selected by crossing chosen keywords. Among these, after careful reading of the titles, 712 papers were considered potential as references. After applying inclusion/exclusion criteria, 50 studies were selected from 132 eligible abstracts. Most studies linked the development and treatment of obesity from epigenetically stimulated metabolic programming during the early stages of pregnancy and life. This review provides theoretical basis to the understanding that the programmed development of childhood obesity may be linked to early exposure to environmental factors, such as (nutrition and regular practice of exercise) and stimulus can epigenetically alter the modulation of the obesogenic metabolic behavior during pregnancy and the developmental stages of children and/or postpone the pathophysiologic disease stage to adulthood.

Abundance of Harpy and Crested Eagles from a reservoir-impact area in the Low- and Mid-Xingu River.

In the Brazilian Amazon, two monospecific genera, the Harpy Eagle and Crested Eagle have low densities and are classified by IUCN as Near Threatened due to habitat loss, deforestation, habitat degradation and hunting. In this study, we evaluate occurrence of these large raptors using the environmental surveys database from Belo Monte Hydroelectric Power Plant. Integrating the dataset from two methods, we plotted a distribution map along the Xingu River, including records over a 276-km stretch of river. Terrestrial surveys (RAPELD method) were more efficient for detecting large raptors than standardized aquatic surveys, although the latter were complementary in areas without modules. About 53% of the records were obtained during activities of wildlife rescue/flushing, vegetation suppression or in transit. Between 2012 and 2014, four Harpy Eagles were removed from the wild; two shooting victims, one injured by collision with power lines and one hit by a vehicle. Also, seven nests were mapped. The mean distance between Harpy Eagle records was 15 km along the river channel, with a mean of 20 km between nests near the channel, which allowed us to estimate 20 possible pairs using the alluvial forest, riverine forest and forest fragments. Territories of another ten pairs will probably be affected by inundation of the Volta Grande channel, which is far from the main river. The average distance between Crested Eagle records was 16 km along the river channel. The only nest found was 1.3 km away from a Harpy Eagle nest. The remnant forests are under threat of being replaced by cattle pastures, so we recommend that permanently protected riparian vegetation borders (APP) be guaranteed, and that forest fragments within 5 km of the river be conserved to maintain eagle populations.

Abundance of Harpy and Crested Eagles from a reservoir-impact area in the Low- and Mid-Xingu River / Abundância de Gavião-real e Gavião-real falso numa área sob impacto de reservatório no Baixo e Médio rio Xingu

In the Brazilian Amazon, two monospecific genera, the Harpy Eagle and Crested Eagle have low densities and are classified by IUCN as Near Threatened due to habitat loss, deforestation, habitat degradation and hunting. In this study, we evaluate occurrence of these large raptors using the environmental surveys database from Belo Monte Hydroelectric Power Plant. Integrating the dataset from two methods, we plotted a distribution map along the Xingu River, including records over a 276-km stretch of river. Terrestrial surveys (RAPELD method) were more efficient for detecting large raptors than standardized aquatic surveys, although the latter were complementary in areas without modules. About 53% of the records were obtained during activities of wildlife rescue/flushing, vegetation suppression or in transit. Between 2012 and 2014, four Harpy Eagles were removed from the wild; two shooting victims, one injured by collision with power lines and one hit by a vehicle. Also, seven nests were mapped. The mean distance between Harpy Eagle records was 15 km along the river channel, with a mean of 20 km between nests near the channel, which allowed us to estimate 20 possible pairs using the alluvial forest, riverine forest and forest fragments. Territories of another ten pairs will probably be affected by inundation of the Volta Grande channel, which is far from the main river. The average distance between Crested Eagle records was 16 km along the river channel. The only nest found was 1.3 km away from a Harpy Eagle nest. The remnant forests are under threat of being replaced by cattle pastures, so we recommend that permanently protected riparian vegetation borders (APP) be guaranteed, and that forest fragments within 5 km of the river be conserved to maintain eagle populations.

Na Amazônia brasileira dois gêneros mono-específicos, Harpia e Morphnus, caracterizam-se por baixa densidade e estão classificados pelo IUCN como Quase Ameaçados, porém ocorrem sobre grande parte do território nacional, suas principais ameaças são a fragmentação florestal, a degradação de hábitat e a caça. Neste estudo avaliamos a abundância destas duas grandes aves de rapina utilizando a base de dados dos programas ambientais da UHE Belo Monte, integrando-se dois métodos para construir um mapa de distribuição ao longo de 245 km do rio Xingu. Os levantamentos terrestres pelo método RAPELD mostraram-se mais eficientes para os registros de grandes águias quando comparado aos esforços padronizados aquáticos, entretanto estes foram complementares na ausência de módulos. Cinquenta e tres por cento foram registros ocasionais durante a supressão da vegetação, afugentamento ou deslocamento. Entre 2012-2014 quatro harpias foram removidas da natureza, dois indivíduos alvo de disparos, uma por colisão com rede elétrica, e outra por atropelamento. Sete ninhos mapeados, a distância média entre os registros de harpia na calha e margens do rio foi de 15 km, 20 km distância média entre ninhos, o que permitiu estimar um total de 20 casais utilizando as florestas aluviais em uma distancia de 270 km, incluindo matas ciliares e os fragmentos fora da margem do rio. Estimamos que territórios de outros 10 casais usando a Volta Grande longe do rio principal também serão afetados pela inundação. A distância média entre os registros de Morphnus foi 16 km ao longo do rio, o único ninho mapeado estava distante 1.3 km do ninho de Harpia. Estes fragmentos florestais estão sendo substituídos por pastagens, ressaltando-se a importância da manutenção das áreas de preservação permanentes (APP) e a proteção destes fragmentos em diversos formatos de áreas de proteção, para diminuir a degradação dos mesmos e garantir a manutenção das populações destes grandes predadores na região do rio Xingu.

An increase in glucose concentration in the lateral ventricles of the brain induces changes in autonomic nervous system activity.

OBJECTIVE: Changes in glucose levels mobilize a neuroendocrine response that prevents or corrects glycemia. The hypothalamus is the main area of the brain that regulates glycemic homeostasis. Metabolic diseases, such as obesity and diabetes, are related to imbalance of this control. The modulation of autonomic nervous system (ANS) activity is mediated by neuronal hypothalamic pathways. In the present work, we investigate whether glucose concentration in the hypothalamic area changes ANS activity. METHODS: Glucose was administered intracerebroventricularly to 90-day-old rats, and samples of blood were collected during brain glucose infusion to measure the blood glucose and insulin levels. The electric activity of the superior vagus nerve and superior sympathetic ganglion was directly registered. RESULTS: Glucose 5·6 mM infused in the hypothalamus induced a 67·6% decrease in blood insulin concentration compared to saline infusion (P<0·01); however, no glycemia changes occurred. During glucose 5·6 mM intracerebroventricular infusion, the firing rate of the vagus nerve was decreased 39% and sympathetic nerve activity was increased 177% compared to saline infusion (P<0·01). DISCUSSION: Glucose injection into the brain in the hypothalamic area modulates glucose homeostasis, which might be mediated by the sensitivity of the hypothalamic area to local changes in glucose concentration. We suggest that gluconeurons in the hypothalamus contribute to the control of glycemia through ANS activity.

Early exposure to a high-fat diet has more drastic consequences on metabolism compared with exposure during adulthood in rats.

The aim of this study was determine whether the introduction of a high-fat diet during the peripubertal phase induces significant changes in body weight control, glucose homeostasis and the parasympathetic tonus compared with the administration of this diet to adult rats. High-fat diet was offered to male Wistar rats at weaning or during adulthood. A group of rats received high-fat diet for 60 days, from weaning to 81-day-old (HF81) or from 60 to 120-day-old (HF120), whereas 2 other groups received a normal-fat diet (i. e., NF81 and NF120). We analyzed adiposity, glucose homeostasis, insulin sensitivity, and vagal nerve activity. High-fat diet increased the accumulation of adipose tissue in all of the rats, but the difference was greater in the rats that were fed the high-fat diet since weaning (p<0.001). The HF rats showed glucose intolerance with high levels of insulin secretion during the glucose tolerance test (p<0.01). Rats that were fed the high-fat diet presented severe insulin resistance, indicated by a low K itt (p<0.01). Interestingly, the HF81 rats exhibited greater insulin resistance compared with the HF120 rats (p<0.05). The recordings of vagus nerve activity showed that the HF rats had higher parasympathetic activity than the NF rats irrespective of age (p<0.01). Our results show that a high-fat diet offered to rats just after weaning or in adulthood both cause impairment of glycemic homeostasis and imbalance in parasympathetic activity. Importantly, the consumption of high-fat diet immediately after weaning has more drastic consequences compared with the consumption of the same diet during adulthood.

Metabolic imprinting by maternal protein malnourishment impairs vagal activity in adult rats.

Protein restriction during lactation has been suggested to diminish parasympathetic activity, whereas sympathetic activity is enhanced in adult rats. The present study analyses whether dysfunction of the autonomic nervous system is involved in the impairment of insulin secretion from perinatally undernourished rats. Male neonates were reared by mothers fed a low- (4%) protein (LP group) or normal- (23%) protein diet (NP group). At 81 days of age, LP rats showed less body mass than NP rats (318 ± 4 g versus 370 ± 5 g) (P < 0.001). Fat tissue accumulation decreased in LP [0.8 ± 0.03 g/100 g body weight (BW)] compared to NP rats (1.1 ± 0.04 g/100 g BW) (P < 0.001). LP were glucose-intolerant as registered by the area under the curve of an i.v. glucose tolerance test (37 ± 3) compared to NP rats (29 ± 2) (P < 0.05); however, LP animals showed fasting normoglycaemia (LP, 5.0 ± 0.1; NP, 4.9 ± 0.03 mm) and hypoinsulinaemia (LP, 0.10 ± 0.02 ng/ml; NP, 0.17 ± 0.02 ng/ml). LP also showed glucose tissue uptake 60% higher than NP rats (P < 0.05). Vagus firing rate from LP was lower (7.1 ± 0.8 spikes/5 s) than that in NP rats (12.3 ± 0.7 spikes/5 s) (P < 0.001); however, there was no difference in sympathetic nervous activity. The cholinergic insulinotrophic effect was lower in pancreatic islets from LP (0.07 ± 0.01 ng/min/islet) than in NP rats (0.3 ± 0.06 ng/min/islet), whereas the levels of adrenaline-mediated inhibition of glucose-induced insulin release were similar. Perinatal protein restriction inhibited the activity of the vagus nerve, thus reducing the insulinotrophic effect of parasympathetic pathways on pancreatic ß-cells, which inhibit insulin secretion.

Label-free prehybridization DNA microarray imaging using photonic crystals for quantitative spot quality analysis.

Technical variability during DNA capture probe printing remains an important obstacle to obtaining high quality data from microarray experiments. While methods that use fluorescent labels for visualizing printed arrays prior to hybridization have been presented, the ability to measure spot density using label-free techniques would provide valuable information on spot quality without altering standard microarray protocols. In this study, we present the use of a photonic crystal biosensor surface and a high resolution label-free imaging detection instrument to generate prehybridization images of spotted oligonucleotide microarrays. Spot intensity, size, level of saturation, and local background intensity were measured from these images. This information was used for the automated identification of missed spots (due to mechanical failure or sample depletion) as well as the assignment of a score that reflected the quality of each printed feature. Missed spots were identified with >95% sensitivity. Furthermore, filtering based on spot quality scores increased pairwise correlation of posthybridization spot intensity between replicate arrays, demonstrating that label-free spot quality scores captured the variability in the microarray data. This imaging modality can be applied for the quality control of printed cDNA, oligonucleotide, and protein microarrays.

Swimming exercise at weaning improves glycemic control and inhibits the onset of monosodium L-glutamate-obesity in mice.

Swimming exercises by weaning pups inhibited hypothalamic obesity onset and recovered sympathoadrenal axis activity, but this was not observed when exercise training was applied to young adult mice. However, the mechanisms producing this improved metabolism are still not fully understood. Low-intensity swimming training started at an early age and was undertaken to observe glycemic control in hypothalamic-obese mice produced by neonatal treatment with monosodium l-glutamate (MSG). Whereas MSG and control mice swam for 15 min/day, 3 days a week, from the weaning stage up to 90 days old, sedentary MSG and normal mice did not exercise at all. After 14 h of fasting, animals were killed at 90 days of age. Perigonadal fat accumulation was measured to estimate obesity. Fasting blood glucose and insulin concentrations were also measured. Fresh isolated pancreatic islets were used to test glucose-induced insulin release and total catecholamine from the adrenal glands was measured. Mice were also submitted to intraperitoneal glucose tolerance test. MSG-obese mice showed fasting hyperglycemia, hyperinsulinemia, and glucose intolerance. Severe reduction of adrenal catecholamines content has also been reported. Besides, the inhibition of fat tissue accretion, exercise caused normalization of insulin blood levels and glycemic control. The pancreatic islets of obese mice, with impaired glucose-induced insulin secretion, were recovered after swimming exercises. Adrenal catecholamine content was increased by swimming. Results show that attenuation of MSG-hypothalamic obesity onset is caused, at least in part, by modulation of sympathoadrenal axis activity imposed by early exercise, which may be associated with subsequent glucose metabolism improvement.

Transplantation of pancreatic islets from hypothalamic obese rats corrects hyperglycemia of diabetic rats.

Pancreatic islets isolated from adult obese rats, obtained by neonatal treatment with monosodium L-glutamate (MSG), oversecrete insulin stimulated by glucose concentration. Whereas adult MSG obese rats are hyperinsulinemic, their pancreatic islets still secrete insulin after high glucose demand. This is crucial so that the animals do not become hyperglycemic. Islets from MSG obese rats were implanted in diabetic donor rats so that the capacity of islets in regulating blood glucose concentration could be evaluated. Hyperglycemic (glucose 22 to 34 mmol/L) rats obtained with streptozotocin (STZ) treatment were used as recipients. Islet donors consisted of control adult and MSG obese rats. Only 600 islets were transplanted via the portal vein to diabetic rats. During 4 days after the transplant, fed blood glucose was monitored. After 12 hours of fasting the rats were killed; their blood samples were used to measure glucose and insulin concentration; retroperitoneal fat pads were isolated and weighed to estimate body fat. Transplanted islets from MSG obese rats decreased of fed glucose levels by 34% in diabetic rats (P < .05); however, glucose levels still remained twofold higher than those of intact controls (P < .05). Similar to MSG islets, islets grafts from control rats provoked the same effects in diabetic rats. High fasting blood glucose and low insulin levels of diabetic rats were corrected by islet grafts. Transplantations were able to recover 40% of fat in diabetic rats. The results demonstrated that islets from MSG obese rats may regulate blood glucose concentrations in diabetic rats, and suggesting that their function was not permanently altered by the onset of obesity.

Swim training applied at early age is critical to adrenal medulla catecholamine content and to attenuate monosodium L-glutamate-obesity onset in mice.

Exercise has been recommended as a remedy against a worldwide obesity epidemic; however, the onset of excessive weight gain is not fully understood, nor are the effects of exercise on body weight control. Activity deficits of the sympathetic nervous system, including the sympathoadrenal axis, have been suggested to contribute to high fat accumulation in obesity. In the present work, swim training was used to observe fat accumulation and adrenal catecholamine stocks in hypothalamic-obese mice produced by neonatal treatment with monosodium L-glutamate (MSG). MSG-treated and normal mice swam for 15 min/day, 3 days a week, from weaning up to 90 days old (EXE 21-90); from weaning up to 50 days old (EXE 21-50) and from 60 up to 90 days old (EXE 60-90). Sedentary MSG and normal mice (SED groups) did not exercise at all. Animals were sacrificed at 90 days of age. MSG treatment induced obesity, demonstrated by a 43.08% increase in epididymal fat pad weight; these adult obese mice presented 27.7% less catecholamine stocks in their adrenal glands than untreated mice (p<0.001). Exercise reduced fat accumulation and increased adrenal catecholamine content in EXE 21-90 groups. These effects were more pronounced in MSG-mice than in normal ones. Halting the exercise (EXE 21-50 groups) still changed fat accretion and catecholamine stocks; however, no effects were recorded in the EXE 60-90 groups. We conclude that metabolic changes imposed by early exercise, leading to an attenuation of MSG-hypothalamic obesity onset, are at least in part due to sympathoadrenal activity modulation.

Cytokines activate genes of the endocytotic pathway in insulin-producing RINm5F cells.

AIMS/HYPOTHESIS: Cytokines are important humoral mediators of beta cell destruction in autoimmune diabetes. The aim of this study was to identify novel cytokine-induced genes in insulin-producing RINm5F cells, which may contribute to beta cell death or survival. METHODS: A global gene expression profile in cytokine-exposed insulin-producing RINm5F cells was achieved by automated restriction fragment differential display PCR. The expression of selected candidate genes was confirmed by real-time RT-PCR analysis. RESULTS: Exposure of RINm5F cells to IL-1beta or to a cytokine mixture (IL-1beta, TNF-alpha, IFN-gamma) for 6 h resulted in the differential expression of a functional gene cluster. Apart from the well-known up-regulation of the cytokine-responsive genes iNOS, NF-kappaB, MnSOD and Hsp70, several genes that belong to the functional cluster of the endocytotic pathway were identified. These endocytotic genes comprised: clathrin, megalin, synaptotagmin and calcineurin, which were up-regulated by IL-1beta or the cytokine mixture. In contrast, the expression of the calcineurin inhibitor CAIN and of the GDP/GTP exchange protein Rab3 was down-regulated by cytokines. Other up-regulated cytokine-responsive genes were: agrin, murine adherent macrophage protein mRNA ( MAMA) and transport-associated protein ( TAP1/MTP), whereas the plasma membrane calcium ATPase ( PMCA) 2 and PMCA 3 genes were down-regulated by cytokines. CONCLUSIONS/INTERPRETATION: Our results indicate that genes of the endocytotic pathway are regulated by pro-inflammatory cytokines. This might affect the density of cytokine receptors at the beta cell surface and concomitantly the sensitivity of the cells to cytokine toxicity. A better understanding of the functional cross-talk between endocytotic and cytokine signalling pathways could further the development of novel strategies to protect pancreatic beta cells against toxic effects of pro-inflammatory cytokines.

Acute effects of fatty acids on insulin secretion from rat and human islets of Langerhans.

Fatty acids have both stimulatory and inhibitory effects on insulin secretion. Long-term exposure to fatty acids results in impaired insulin secretion whilst acute exposure has generally been found to enhance insulin release. However, there are conflicting data in the literature as to the relative efficacy of various fatty acids and on the glucose dependency of the stimulatory effect. Moreover, there is little information on the responses of human islets in vitro to fatty acids. We have therefore studied the acute effects of a range of fatty acids on insulin secretion from rat and human islets of Langerhans at different glucose concentrations. Fatty acids (0.5 mM) acutely stimulated insulin release from rat islets of Langerhans in static incubations in a glucose-dependent manner. The greatest effect was seen at high glucose concentration (16.7 mM) and little or no response was elicited at 3.3 or 8.7 mM glucose. Long-chain fatty acids (palmitate and stearate) were more effective than medium-chain (octanoate). Saturated fatty acids (palmitate, stearate) were more effective than unsaturated (palmitoleate, linoleate, elaidate). Stimulation of insulin secretion by fatty acids was also studied in perifused rat islets. No effects were observed at 3.3 mM glucose but fatty acids markedly potentiated the effect of 16.7 mM glucose. The combination of fatty acid plus glucose was less effective when islets had been first challenged with glucose alone. The insulin secretory responses to fatty acids of human islets in static incubations were similar to those of rat islets. In order to examine whether the responses to glucose and to fatty acids could be varied independently we used an animal model in which lactating rats are fed a low-protein diet during early lactation. Islets from rats whose mothers had been malnourished during lactation were still able to respond effectively to fatty acids despite a lowered secretory response to glucose. These data emphasise the complex interrelationships between nutrients in the control of insulin release and support the view that fatty acids play an important role in glucose homeostasis during undernutrition.

Parasympathetic activity changes insulin response to glucose and neurotransmitters.

Pancreatic islet isolated from hyperinsulinemic obese rodents showed high glucose sensitivity to stimulation of insulin secretion. Current research evaluates the effect of subdiaphragmatic vagotomy on insulin secretion stimulated by glucose and by a cholinergic agonist carbachol (Cch) in islets isolated from monosodium L-glutamate (MSG)-obese rats. During the first 5 days after birth, MSG was intradermically injected into the cervical area of male Wistar rats (n=26). Control animals were injected with hyperosmotic saline solution (n=26). Vagotomy was performed on 30-day-old rats. On the 90th day, after a 12-h fast, the animals were killed. Pancreatic islets were isolated by collagenase. Batches of islets (n=30) were incubated for 60 min in glucose 2.8-20.0 mM or 0.1-2.0 mM Cch in the presence of glucose 8.3 mM. Released insulin was measured by radioimmunoassay. Insulin secretion stimulated by glucose in islets from MSG-obese rats shifted to the left when compared to that of controls, 63.8+/-3.9 and 42.2+/-2.6 ng/ml/islet/60 min (p<0.001), respectively. Vagotomy decreased by 56% (p<0.001) the secretion induced by all glucose concentrations in islets from MSG-obese rats. In the controls the operation caused a 30% (p<0.01) reduction. Cch stimulated insulin secretion in normal and obese rat islets. Response to obese rat islets was 1/3 less than normal ones (p<0.05). Vagotomy produced a greater potentiation of Cch induced insulin secretion on islets from obese rats. Data suggested that parasympathetic modulation is important to insulin secretion control.

Effects of decrease of extracellular sodium in carbachol-evoked catecholamine secretion in isolated adrenal medullae of rats.

The effect of extracellular Na(+) deprivation on the carbachol-evoked catecholamine secretion was evaluated in chromaffin cells. Isolated adrenal medullae of male Wistar rats were incubated in solutions with different sodium concentrations (144,0; 75,0; 25,0 and psi mM). Catecholamine secretions inversely increased as a response to fall of extracellular concentration of sodium. The magnitude of response to cholinergic stimulus (carbachol 100 microM) was decreased in low extracellular sodium concentration. Atropine (100 microM) inhibited secretion of catecholamine induced by carbachol in the presence and in the absence of extracellular sodium. Results suggest that in isolated adrenal medullae of rats (1) decrease in concentration of extracellular sodium increases secretion of catecholamines, perhaps by a greater influx of calcium from the extracellular environment through reversal of Na(+) /Ca(2+) exchanger; (2) intensity of catecholamine secretion induced by cholinergic stimulus seems to depend on extracellular sodium.

Insulin secretion and acetylcholinesterase activity in monosodium l-glutamate-induced obese mice.

OBJECTIVE: Pancreatic islets isolated from mice treated neonatally with monosodium L-glutamate (MSG) were used to study insulin secretion. MATERIALS AND METHODS: Total acetylcholinesterase (AchE) activity of tissue extract was measured as a cholinergic activity marker. Obesity recorded in 90-day-old MSG mice (OM) by Lee index reached 366.40 +/- 1.70, compared to control mice (CM) 324.40 +/- 1.10 (p < 0.0001). Glucose 5.6 mM induced insulin secretion of 36 +/- 5 pg/15 min from islets of CM and 86 +/- 13 from OM (p < 0.001). When glucose was raised to 16.7 mM, islets from OM secreted 1,271 +/- 215 and 1,017 +/- 112 pg/30 min to CM. AchE activity of pancreas from OM was 0.64 +/- 0.02 nmol of substrate hydrolyzed/min/mg of tissue and 0.52 +/- 0.01 to CM (p < 0.0001). Liver of obese animals also presented increase of AchE activity. RESULTS: These indicate that OM insulin oversecretion in low glucose may be attributed, at least in part, to an enhancement of parasympathetic tonus.

Vagotomy reduces obesity in MSG-treated rats.

In order to study the role of vagus nerve activity at the onset of obesity induced by monosodium glutamate (MSG), 30-day-old MSG-rats were vagotomized or sham operated. Body weight and food intake were recorded until animals were 90 days old and then sacrificed. Naso-anal length was recorded for all animals. Periepididymal and retroperitoneal fat pads were isolated and weighed. Reduction of body weight and naso-anal length were registered in 30-day-old MSG-rats. Obesity could also be observed, as increase of Lee index indicated. Results were most evident in 90-day-old MSG-rats. In both groups neither body weight gain nor food intake was changed by vagotomy. However, fat accumulation on tissues was reduced by vagotomy in MSG-rats. The results showed that MSG-obesity is not related to an increment in food intake behavior. Vagotonia might play a role at the onset of MSG-obesity.

Low protein diets administered to lactating rats affect in a time-dependent manner the development of young.

The effects of diets with different protein levels were evaluated when given at different intervals to lactating rats. Food intake by the litter and weight gain by the young are investigated. From the time of birth, groups of five litters were fed with commercial diet (23% protein) or with semi-synthetic diets (4,8,12 and 16% protein) during the 1st, 1st and 2nd, or 1st, 2nd and 3rd weeks of lactation. After weaning, the young of dams, which were fed hypoprotein diets (4 and 8%), showed less food intake capacity, reduced growth capacity and, in adult life, low body weight in comparison to animals raised on commercial ration with higher protein contents. 12 and 16% protein diets did not cause any change in feeding behavior or in weight development as opposed to the 4 and 8% protein diets. Results suggest that the effects of early undernourishment are time-dependent and may cause irreversible changes in the regulation of metabolism and pathogenesis.

Glucose does not affect catecholamine stimulus-secretion coupling in rat adrenal medulla: relationship to low changes in osmolarity and to insulin.

Glucose levels were analyzed to see whether they directly affect the catecholamine release from chromaffin cells. We incubated isolated adrenal medullae of rats in Krebs-Hepes modified solutions with several glucose concentration, in the presence and absence of carbachol or insulin. Transfer of the medulla from a solution with 11.1 mM of glucose to a 0.56 mM one caused an increase in catecholamine secretion. Relative increase in change of glucose levels from 25 to 0.56 mM and from 50 to 0.56 mM enhanced the effect mentioned above. An inhibitory effect was detected after transfer of the medulla from 0.56 mM to 50 mM glucose. However, correction of solution osmolarity with mannitol or NaCl switched back catecholamine secretion to basal levels in all groups, and correction of solution osmolarity with sucrose indicated an impairment of catecholamine release. No difference was observed in stimulated catecholamine secretion (100 microM of carbachol) at all glucose levels. Further, the presence of insulin did not affect catecholamine secretion in all groups. Our results suggest that in isolated adrenal medullae of rats (1) glucose or variations in glucose levels do not affect catecholamine released; (2) isolated adrenal medulla of rat was highly sensitive to hyperosmolarity and extremely sensitive to hyposmolarity; (3) Insulin had no acute direct effect on catecholamine secretion in isolated adrenal medullae of rats.