Differential sympathetic and angiotensinergic responses in rats submitted to low- or high-salt diet.

The present study was designed to evaluate, in Wistar rats, the effect of high- or low-salt diet on the hemodynamic parameters and on the renal and lumbar sympathetic nerve activity. The renal gene expression of the renin angiotensin system components was also evaluated, aiming to find some correlation between salt intake, sodium homeostasis and blood pressure increase. Male Wistar rats received low (0.06% Na, TD 92141-Harlan Teklad), a normal (0.5% Na, TD 92140), or a high-salt diet (3.12% Na, TD 92142) from weaning to adulthood. Hemodynamic parameters such as cardiac output and total peripheral resistance, and the renal and lumbar sympathetic nerve activity were determined (n=45). Plasma renin activity, plasma and renal content of angiotensin (ANG) I and II, and the renal mRNA expression of angiotensinogen, renin, AT1 and AT2 receptors were also measured (n=24). Compared to normal- and low-salt diet-, high-salt-treated rats were hypertensive and developed an increase (P<0.05) in total peripheral resistance and lumbar sympathetic nerve activity. A decrease in renal renin and angiotensinogen-mRNAs and in plasma ANG II and plasma renin activity was also found in salt overloaded animals. The renal sympathetic nerve activity was higher (P<0.05) in low- compared to high-salt-treated rats, and was associated with an increase (P<0.05) in renal ANG I and II and with a decrease (P<0.05) in AT2 renal mRNA. Plasma ANG I and II and plasma renin activity were higher in low- than in normal-salt rats. Our results show that increased blood pressure is associated with increases in lumbar sympathetic nerve activity and total peripheral resistance in high-salt-treated rats. However, in low-salt-treated rats an increase in the renal sympathetic nerve was correlated with an increase in the renal content of ANG I and II and with a decrease in AT2 renal mRNA. These changes are probably in favor of the antinatriuretic response and the sodium homeostasis in the low-salt group.

Inflamação do parênquima pulmonar na asma e sua relação com as vias aéreas / Pulmonary parenchyma inflammation in asthma

A inflamação da asma não está limitada às vias aéreas e pode comprometer também o parênquima pulmonar periférico, no entanto, não há estudos na literatura que enfoquem a participação do parênquima pulmonar na asma. Objetivo: Caracterizar o infiltrado inflamatótrio do parênquima peribronquiolar e distal em vítimas de asma fatal, comparando-o ao de outras regiões de vias aéreas e a de tecido pulmonar de não asmáticos. Fragementos de tecido pulmonar obtidos de 20 pacientes com asma fatal e 10 controles, necropsiados no Serviço de verificacão de óbito da capital - São Paulo, foram submetidos a estudo de imuno-histoquímica e marcados com anticorpos anti-proteína básica principal (eosinófilos), anti-triptase (mastócitos), anti-elastase neutrofílica (neutrófilos) e anti-marcadores de superfície de linfócitos (CD3, CD$, CD* e CD20). Foram determinadas as densidades celulares no parênquima pulmonar periférico peribronquiolar e distal e nas áreas interna e externa das vias aéreas de grande e de pequeno calibre. Resultados: A densidade de eosinófilos foi significativamente maior nas duas regiões do parênquima pulmonar de asmáticos comparados aos controles, bem como as vias aéreas (p<0,02). Nos pacientes asmáticos a densidade eosinófilica se mostrou menos no parênquima distal em relação à da área interna da via aérea grande apenas (p<0,01). A densidade dos mastócitos foi maior no parênquima peribronquiolar bem como na área externa das vias aéreas de grande e de pequeno calibre de asmáticos comparados aos controles (p<0.04). Diferenças significativas quanto à densidade de linfócitos se restringiram às vias aéreas de asmáticos comparadas as de controles. Maior densidade de neutrófilos foi observada apenas no parênquima pulmonar de asmáticos (p=0.029). Conclusões: O parênquima pulmonar participa do processo inflamatório na asma fatal com aumento de células efetoras (mastócitos, neutrófilos e eosinófilos). A área externa da via aérea foi a região que melhor diferenciou o asmáticodo controle e com o maior número de diferenças significativas. A inflamação do parênquima peribronquiolar, associado ao da área externa da via áerea pequena, reforça o papel do pulmão distal na patofisiologia da asma.

Deficit in hippocampal long-term potentiation in monosodium glutamate-treated rats.

Rats subjected to monosodium glutamate (MSG) administration during the neonatal period present chronic neuroendocrine dysfunction associated with marked cognitive deficits. Long-term potentiation (LTP) in the hippocampus provides a model suited for the study of mammalian brain plasticity and memory formation. In the present work, we used the LTP protocol to investigate the synaptic plasticity in the hippocampal CA1 area of adult rats subjected to MSG treatment during the first 10 days of life. Synaptic transmission in CA1 area was analyzed using extracellular field recordings in response to Schaffer's collateral fiber stimulation in hippocampal slices. Animals injected with MSG exhibited a dramatic decrement of LTP field excitatory postsynaptic potentials (fEPSPs) compared to control group. Analysis of percent enhancement of fEPSP slope at 2 min after high frequency stimulation (HFS) increased by 189.3 +/- 33.2% in slices from control rats and 129.45 +/- 18.5% (p < 0.01) in slices from MSG-treated rats. Additionally, MSG-treated animals failed to maintain or consolidate LTP as revealed by a significant reduction in fEPSP slope enhancement over time after HFS. The mean fEPSP slope, 60 min after HFS, was 154.28 +/- 21% of the average baseline slope in control slices versus only 124.4 +/- 15% in MSG-treated rats (p < 0.01). At 90 min after HFS, slices from controls reached a potentiation of 44.5 +/- 2.9%, whereas the MSG group displayed an overall response enhancement of 17.65 +/- 2.7% of basal levels (p < 0.01). These findings indicate that MSG-treated rats display a chronic impairment of CA1 synaptic plasticity.

The rise of the plasma lipid concentration elicited by dietary sodium chloride restriction in Wistar rats is due to an impairment of the plasma triacylglycerol removal rate.

Studies in humans have indicated that dietary salt restriction raises plasma levels of total cholesterol (TC) and triacylglycerols (TAG). In order to explain the mechanisms involved, a rat experimental model was developed consisting of chronic feeding ad libitum isocaloric diets with variable sodium chloride contents. Rates of synthesis of plasma TAG were measured either as the increase of plasma TAG after blocking its removal from plasma by the intra-arterial pulse infusion of Triton-WR 1339, or as the plasma rate of incorporation of [(14)C]-oleic acid [(14)C]-TAG. Plasma TAG removal rate was determined by the intra-arterial pulse infusion of a lipid emulsion. Severe salt restriction increased the plasma concentrations of TAG (71%) and of TC (10%). This result was not due to modification of the rate of synthesis of plasma TAG but was attributed to a 55% slower rate of removal of the TAG-containing lipoproteins. An increased plasma non-esterified fatty acid concentration, probably due to a salt restriction-related insulin resistance, may have impaired the activity of the enzyme lipoprotein lipase.

Decreased lipolysis and enhanced glycerol and glucose utilization by adipose tissue prior to development of obesity in monosodium glutamate (MSG) treated-rats.

OBJECTIVE: To determine the metabolic alterations that lead to the neonatal administration of monosodium glutamate (MSG), which results in arrested growth and obesity. ANIMALS AND DESIGN: Wistar rats were injected 5 times, every other day, with 4 g of MSG/kg b.w. or with hyperosmotic saline (controls), within the first 10 days of life, and were studied at the age of 30 days. RESULTS: Body weight was lower, whereas adipocyte lipid content, cell diameter, surface area and volume were higher in MSG rats than in controls. Plasma glucose, insulin, NEFA, glycerol and triglyceride levels, and in vitro production of NEFA by lumbar fat pad pieces incubated under basal conditions or in the presence of epinephrine and epinephrine plus glucose in the media were lower in MSG than in control rats. In the same fat pad pieces, the conversion of 1-14C-glycerol into fatty acids was always enhanced and its conversion into glyceride glycerol was enhanced when incubations were carried out in the presence of epinephrine or glucose. Both the hormone sensitive lipase activity and mRNA expression were lower in adipose tissue from MSG rats. Besides, the number of insulin receptors, lipid synthesis from U14C glucose, 3H-2-deoxy D-glucose uptake and cellular GLUT4 translocation index were higher in adipocytes from MSG rats than from the controls. CONCLUSION: It is proposed that an enhanced insulin sensitivity in 1 month old MSG rats is responsible for the decreased lipolytic activity and enhanced glucose uptake. In addition, the enhanced lipogenesis and glycerol reutilization seen in their adipose tissue, disturbs the normal balance between fat depots breakdown and accumulation in favor of the latter.

High- or low-salt diet from weaning to adulthood: effect on insulin sensitivity in Wistar rats.

Because of conflicting results in the literature, further studies are needed to confirm an association between the degree of salt consumption and insulin sensitivity. The aim of this study was to measure insulin sensitivity in rats fed from weaning to adulthood with a low (LSD), normal (NSD), or high (HSD) salt diet. Body weight, carcass lipid content, blood glucose, nonesterified fatty acids, plasma insulin, plasma renin activity, and a glucose transporter (GLUT4) were measured. A euglycemic hyperinsulinemic clamp was used in 52 anesthetized rats. Body weight was higher in rats on LSD than in those on NSD (P<0.05) or HSD (P<0.001). Percentage fat carcass content was higher (P<0.05) in rats on LSD than in those on NSD. Basal plasma insulin and glucose levels were not altered (P>0.05) by salt consumption. Nonesterified fatty acids were lower in rats on HSD than in those on LSD (P<0.05) or NSD (P<0.01). Glucose uptake was lower in rats on LSD than in those on NSD (P<0.05) or HSD (P<0. 001). When a euglycemic hyperinsulinemic clamp was used on pair-weight rats, similar results were obtained, which suggests that the effect of LSD on insulin sensitivity was not due to higher body weight. GLUT4 in insulin-sensitive tissues was increased in rats on HSD except in the cardiac muscle. Captopril treatment partially reversed low insulin sensitivity in LSD rats, whereas losartan did not change it, which indicates that the effect of LSD on insulin sensitivity is angiotensin independent. In conclusion, the present results demonstrate that chronic dietary salt restriction induces a decrease in insulin sensitivity not associated with renin-angiotensin system activity or body weight changes.

Effects of continuous exposure to light on behavioral dopaminergic supersensitivity.

BACKGROUND: This study examines the effects of long-term continuous exposure to light on dopaminergic supersensitivity induced by repeated treatment with haloperidol in rats. METHODS: Spontaneous general activity in an open-field (SGA) and stereotyped behavior induced by apomorphine (SB-APO) or amphetamine (SB-AMP) were used as experimental parameters. Rats were allocated to four groups in each experiment: saline-treated animals kept under a 12-hour light/dark cycle (LD) or 24-hour light/light cycle (LL), and 2 mg/kg haloperidol-treated animals kept under the above cycles. Plasma corticosterone concentration was also measured by radioimmunoassay in saline-treated rats kept under a LD or LL cycle. RESULTS: All the behavioral parameters used showed the development of central dopaminergic supersensitivity in rats kept under both cycles. Continuous exposure to light enhanced SGA and SB-AMP in both saline- and haloperidol-treated rats, but did not modify SB-APO. Animals kept under the LL cycle presented an increased plasma corticosterone concentration. CONCLUSIONS: Our results suggest that continuous exposure to light leads to an increase in dopaminergic function in both normal and "supersensitive" rats. This effect seems to be mediated by a presynaptic mechanism possibly involving corticosterone actions.

Neonatal monosodium glutamate treatment alters rat intestinal muscle reactivity to some agonists.

The following study is an investigation of the changes in the contractile reactivity of visceral muscles in response to agonists and alterations in metabolic parameters after neonatal rat treatment with monosodium-L-glutamate. This treatment markedly sensitizes ileum and colon preparations to adenosine-5'-triphosphate (ATP) stimulation and also increases the colon activity to acetylcholine (p<0.05). Response to bradykinin remained unchanged, while ileum activity to angiotensin II was characterized by a reduction in the maximal tension (E(max)) and an increase in the EC(50) (p<0.05) value. The responses of nonintestinal muscle preparations from monosodium-glutamate-treated rats to both ATP and bradykinin did not show a significant difference when compared to the controls. This treatment diminished food intake, feces excretion and increased plasma insulin, nonesterified fatty acids and triglyceride concentrations (p<0.001). These results suggest that the changes in intestinal muscle activity, in response to agonists, can be due to metabolic alterations as well as the monosodium glutamate action on enteric neurons and/or smooth muscle receptors.

Hormonal and metabolic adaptations to fasting in monosodium glutamate-obese rats.

The effect of fasting on hormonal and metabolic variables was evaluated in normal rats and in rats with obesity induced by neonatal treatment with monosodium glutamate (MSG). The hyperinsulinemia of the fed obese rats was reversed by fasting. Plasma corticosterone was also high in the fed obese and decreased to levels similar to fed controls, while it increased in the latter group during fasting. In contrast, thyroid hormone levels decreased in controls but increased in the obese rats in response to fasting. The fed obese group had lower carcass protein and higher carcass lipid contents than controls. In response to fasting, the decrements of the initial amount of both protein and fat were lower in MSG than in controls. Fasting induced a sustained increase in plasma free fatty acids only in the obese rats, although a single 100 mumol.l-1 dose of norepinephrine stimulated in vitro glycerol release more pronouncedly in epididymal adipocytes from control than obese rats. The results indicate that MSG-obese rats were able to mobilize fat stores during prolonged fasting. The high availability of lipid fuels and the sharp and sustained decrease in circulating corticosterone in the MSG group were probably important in diminishing body protein consumption during fasting.

Ligation of the left renal vein in epm1-Wistar rats: functional and morphologic alterations in the kidneys, testes and suprarenal glands.

OBJECTIVE: The ligation of the left renal vein (LLVR) in man is a controversial procedure in view of the risks of lesion to the renal parenchyma. With the objective of studying the morphologic and functional alterations caused by these lesions, we conducted experimental research with rats. MATERIAL AND METHODS: 64 male adult EPM1-WISTAR rats were used, divided into 8 groups-4 for LLRV and four for control. Each LLRV group and corresponding control group were sacrificed progressively on the 7th, 15th, 30th and 60th day after the initial surgery. RESULTS: We found morphofunctional alterations only in animals that underwent LLRV in the four periods of sacrifice. The proteinuria creatinine in serum, testosterone in serum and serum corticosterone in serum showed practically no alteration in relation to the normal values for rats. Statistically significant severe histological lesions were found in the kidneys and testes of the LLRV groups. Lesions in the suprarenal glands were also present in these groups, but no sufficient to demonstrate statistical significance. CONCLUSION: Based on these results we can conclude that the ligation of the left renal vein is a procedure of high risk in these animals.

Monosodium glutamate (MSG)-obese rats develop glucose intolerance and insulin resistance to peripheral glucose uptake.

Different levels of insulin sensitivity have been described in several animal models of obesity as well as in humans. Monosodium glutamate (MSG)-obese mice were considered not to be insulin resistant from data obtained in oral glucose tolerance tests. To reevaluate insulin resistance by the intravenous glucose tolerance test (IVGTT) and by the clamp technique, newborn male Wistar rats (N = 20) were injected 5 times, every other day, with 4 g/kg MSG (N = 10) or saline (control; N = 10) during the first 10 days of age. At 3 months, the IVGTT was performed by injecting glucose (0.75 g/kg) through the jugular vein into freely moving rats. During euglycemic clamping plasma insulin levels were increased by infusing 3 mU.kg-1.min-1 of regular insulin until a steady-state plateau was achieved. The basal blood glucose concentration did not differ between the two experimental groups. After the glucose load, increased values of glycemia (P < 0.001) in MSG-obese rats occurred at minute 4 and from minute 16 to minute 32. These results indicate impaired glucose tolerance. Basal plasma insulin levels were 39.9 +/- 4 microU/ml in control and 66.4 +/- 5.3 microU/ml in MSG-obese rats. The mean post-glucose area increase of insulin was 111% higher in MSG-obese than in control rats. When insulinemia was clamped at 102 or 133 microU/ml in control and MSG rats, respectively, the corresponding glucose infusion rate necessary to maintain euglycemia was 17.3 +/- 0.8 mg.kg-1.min-1 for control rats while 2.1 +/- 0.3 mg.kg-1.min-1 was sufficient for MSG-obese rats. The 2-h integrated area for total glucose metabolized, in mg.min.dl-1, was 13.7 +/- 2.3 vs 3.3 +/- 0.5 for control and MSG rats, respectively. These data demonstrate that MSG-obese rats develop insulin resistance to peripheral glucose uptake.

Monosodium glutamate (MSG) - obese rats develop glucose intolerance and insulin resistance to peripheral glucose uptake

Different levels of insulin sensitivity have been descrebed in several animal models of obesity as well as in humans. Monosodium glutamate (MSG)-obese mice were considered not be insulin resistant from data obtained in oral glucose tolerance tests. To reevaluate insulin resistance by the intravenous glucose tolerance test (IVGTT) and by the clamp technique, newborn male Wistar rats (N = 20) were injected 5 times, every other day, with 4 g/Kg MSG (N = 10) or saline (control; N = 10) during the first 10 days of age. At 3 months, the IVGTT was performed by injecting glucose (0.75 g/Kg) through the jugular vein into freely moving rats. During euglycemic clamping plasma insulin levels were increased by infusing 3 mU. Kg(-1). min (-1) of regular insulin until a steady-state plateau was achieved. The basal blood glucose concentration did not differ between the two experimental groups. After the glucose load, increased values of glycemia (p<0.001) in MSG-obese rats occurred at minute 4 and from minute 16 to minute 32. These results indicate impaired glucose tolerance. Basal plasm insulin levels were 39.9 + 4 muU/ml in control and 66.4 + 5.3 muU/ml in MSG-obese rats. The mean post-glucose area increase of insulin was 111 percent higher in MSG-obese than in control rats. When insulinemia was clamped, at 102 or 133 muU/ml in control and MSG rats, respectively, the corresponding glucose infusion rate necessary to maintain euglycemia was 17.3 + 0.8 mg. kg (-1). min(-1) for control rats while 2.1 + 0.3 mg. kg(-1). min(-1) was sufficient for MSG-obese rats. The 2-h integrated area for total glucose metabolized, in mg. min. dl(-1), was 13.7 + 2.3 vs 3.3 + 0.5 for control and MSG rats, respectively. These data demonstrate that MSG-obese rats develop insulin resistance to peripheral glucose uptake.

Effect of chemical stimulation of the dorsomedial hypothalamic nucleus on blood plasma glucose, triglycerides and free fatty acids in rats.

The effects of chemical stimulation of the dorsomedial hypothalamic nucleus (DMH) on blood plasma concentration of glucose, triglycerides, insulin, and free fatty acids (FFA) were investigated in anesthetized adult Wistar rats. Microinjection of 12.5 nmol of norepinephrine into the DMH increased blood plasma concentration of glucose and FFA, decreased triglycerides, and did not change plasma insulin within 5 min; after 20 min, blood glucose and FFA reached control values. Microinjection of epinephrine (12.5 nmol) into the DMH also increased blood plasma glucose concentration and decreased triglycerides after 5 min. These effects are probably mediated by beta-adrenergic mechanisms, because they were prevented by beta-adrenergic antagonist propranolol, but not by alpha-adrenergic antagonist prazosin. Microinjection into the DMH of glutamate, dopamine, or acetylcholine failed to cause any change in those metabolic parameters, corroborating the hypothesis that the DMH is part of a beta-adrenergic pathway involved in short-term modulation of the availability of glucose and FFA.

Ultra-sonografia seriada do endométrio e da endocérvice durante o ciclo menstrual normal da mulher / Serial ultrasonography of the endometrium and endocervix during the normal menstrual cycle of women

Os relatos ultra-sonográficos do endométrio humano säo, em sua maior parte, obtidos de pacientes com esterilidade conjugal, nulíparas, fazendo uso de drogas indutoras da ovulaçäo. Essas pesquisas, geralmente, näo se acompanham do estudo histológico da cavidade uterina e preocupam-se, sobretudo, com o período ovulatório. Há, contudo, controvérsias na interpretaçäo das imagens. OBJETIVO. Estudas a ultra-sonografia do endométrio, no decorrer do ciclo menstrual normal. MÉTODOS. Os autores selecionaram 15 mulheres, eumenorréicas, multíparas, que näo faziam uso de drogas indutoras da ovulaçäo, DIU ou contra-conceptivos hormonais. todas foram examinadas no primeiro, no sétimo, no décimo-quarto eno vigésimo-primeiro dia do ciclo menstrual. Confrontaram-se os achados ecográficos com os resultados histológicos. RESULTADOS. Avaliaram a imagem ultra-sonográfica do endométrio em 66.66 por cento das mulheres no primeiro dia do ciclo. Em todas elas, no sétimo, décimo-quarto e vigésimo-primeiro dia essa imagem também pôde ser identificada e apreciada. Verificaram, durante o ciclo, aumento progressivo da espessura da imagem endometrial, de forma linear. O halo hipoecóico teveincidência progressiva, atingindo 93,33 por cento no vigésimo-primeiro dia do ciclo. CONCLUSÄO. As alteraçöes cíclicas do endométrio foram demonstradas pela ultra-sonografia. As modificaçöes endocervicais também foram detectadas. Todavia, säo menos exuberantes do que as observadas no endométrio

[Serial ultrasonography of the endometrium and endocervix during the normal menstrual cycle in women]. / Ultra-sonografia seriada do endométrio e da endocérvice durante o ciclo menstrual normal da mulher.

Articles on ultrasound of the human endometrium are in the majority of the cases based on studies of patients who have infertility and are taking drugs to induce ovulation. Such investigations do not include histological study of the endometrium and have focused on the ovulatory period. There is controversy in the interpretation of the images. PURPOSE--To evaluate the sonographic appearance of the endometrium during the normal menstrual cycle. METHODS--We studied 15 multiparous women with normal cycles, and who were not under drugs for ovulation induction, had neither IUD, nor were having oral hormonal contraceptives. They were seen on the first, seventh, fourteenth, and twentieth-first days of the menstrual cycle. The sonographic aspects were compared with the histological findings. RESULTS--We could see the images of the endometrium on the first day of the cycle in 66.66% of the patients. On the other visits we could study properly its features very well in all the patients. The endometrial image thickness increased in a linear pattern and the hypoechogenic halo was seen in 93.33% of the patients on the twentieth-first day of the menstrual cycle. CONCLUSION--The cyclic changes of the endometrium were shown with the sonography. The cyclic changes of the endocervix were evaluated too with the sonogram although they are not as remarkable as the endometrial ones.

Neonatal monosodium glutamate treatment increases epididymal adipose tissue sensitivity to insulin in three-month old rats.

We determined the response of glucose transport to insulin in isolated adipocytes and the lipogenic activity of insulin in fragments of epididymal adipose tissue obtained from male MSG-obese rats. Basal glucose transport rates (pmol 3 min-1 10(5) cells-1) were 100% higher in MSG than in control cells (3-month old male Wistar rats) pre-incubated for 30 min (P < 0.01). Nevertheless, when expressed as fmol 3 min-1 microns 2 cell surface area-1, transport rates were similar for the two groups (31.2 +/- 2.6 for MSG and 26.5 +/- 3.2 for controls, N = 7). No differences were observed in maximally insulin-stimulated glucose transport rates between groups (72.6 +/- 10.6 for MSG and 101.0 +/- 12.0 for controls, N = 7). In contrast, for adipocytes pre-incubated for 2 h, the basal uptake rates were 3.7 times higher and the maximal response to insulin was 103% higher in cells from MSG rats compared to control cells. These alterations in MSG rat adipocytes were accompanied by changes in cell sensitivity to insulin (EC50, 0.13 +/- 0.02 ng/ml for MSG vs 0.46 +/- 0.10 ng/ml for controls, P < 0.01). The rates of incorporation of labelled substrates (3H2O and 14C-glucose) into total lipids showed that in vitro lipogenesis was also 79% (3H2O) and 250% (14C-glucose) higher in MSG adipose tissue fragments. The MSG animals were consistently hyperinsulinemic. These data suggest that the obesity of 3-month old MSG rats is a metabolic alteration characterized by an enhanced adipocyte capacity to transport glucose and to synthetize lipids resulting in increased insulin sensitivity.

Neonatal monosodium glutamate treatment increases epididymal adipose tissue sensitivity to insulin in three-month old rats

We determined the response of glucose transport to insulin in isolated adipocytes and the lipogenic activity of insulin in fragments of epididymal adipose tissue obtained from male MSG-obese rats. Basal glucose transport rates (pmol 3 min-1 10(5) cells-1) were 100 higher in MSG than in control cells (3-month old male Wistar rats) pre-incubated for 30 min (P < 0.01). Nevertheless, when expressed as fmol 3 min-1 microns 2 cell surface area-1, transport rates were similar for the two groups (31.2 +/- 2.6 for MSG and 26.5 +/- 3.2 for controls, N = 7). No differences were observed in maximally insulin-stimulated glucose transport rates between groups (72.6 +/- 10.6 for MSG and 101.0 +/- 12.0 for controls, N = 7). In contrast, for adipocytes pre-incubated for 2 h, the basal uptake rates were 3.7 times higher and the maximal response to insulin was 103 higher in cells from MSG rats compared to control cells. These alterations in MSG rat adipocytes were accompanied by changes in cell sensitivity to insulin (EC50, 0.13 +/- 0.02 ng/ml for MSG vs 0.46 +/- 0.10 ng/ml for controls, P < 0.01). The rates of incorporation of labelled substrates (3H2O and 14C-glucose) into total lipids showed that in vitro lipogenesis was also 79 (3H2O) and 250 (14C-glucose) higher in MSG adipose tissue fragments. The MSG animals were consistently hyperinsulinemic. These data suggest that the obesity of 3-month old MSG rats is a metabolic alteration characterized by an enhanced adipocyte capacity to transport glucose and to synthetize lipids resulting in increased insulin sensitivity.

The regulation of insulin action in isolated adipocytes. Role of the periodicity of food intake, time of day and melatonin.

Isolated adipocytes from rats submitted to four weeks of ad libitum feeding (AL) or meal feeding (MF, 2 h/22 h, feeding/fasting, meal time: 8:00-10:00 a.m.) schedules or pre-incubated with or without melatonin (0, 1 nM, 10 nM, 100 nM) for 5 h were submitted to insulin-stimulated [3H]-2-deoxyglucose (0.1 mM, 0.12 microCi) uptake rate measurements and insulin binding assays. Insulin sensitivity was defined as the hormone concentration capable of producing the half-maximal transport rate. Insulin sensitivity varied depending on the previous conditions of the adipocytes. In MF animals, adipose cells were more sensitive (EC50 = 0.175 ng/ml) just at the moment of the expected meal. In AL rats, sensitivity was lower (EC50 = 0.678 ng/ml) at 8:00 a.m. and increased (EC50 = 0.398 ng/ml) at 4:00 p.m. These data clearly implicate the expectation of food and period of the day with the regulation of insulin action. All these modifications in sensitivity occurred without any change in insulin receptor number or affinity. Melatonin, a secretory product of the pineal gland, induced an increase in cell sensitivity to insulin in adipocytes incubated with the highest hormone concentration (100 nM). We conclude that factors related to feeding training and circadian rhythmicity modulate cell sensitivity to insulin.

The regulation of insulin action in isolated adipocytes. Role of the periodicity of food intake, time of day and melatonin

Isolated adipocytes from rats submitted to four weeks of ad libitum feeding (AL) or meal feeding (MF, 2 h/22 h, feeding/fasting, meal time: 8:00-10:00 a.m.) schedules or pre-incubated with or without melatonin (0, 1 nM, 10 nM, 100 nM) for 5 h were submitted to insulin-stimulated [3H]-2-deoxyglucose (0.1 mM, 0.12 microCi) uptake rate measurements and insulin binding assays. Insulin sensitivity was defined as the hormone concentration capable of producing the half-maximal transport rate. Insulin sensitivity varied depending on the previous conditions of the adipocytes. In MF animals, adipose cells were more sensitive (EC50 = 0.175 ng/ml) just at the moment of the expected meal. In AL rats, sensitivity was lower (EC50 = 0.678 ng/ml) at 8:00 a.m. and increased (EC50 = 0.398 ng/ml) at 4:00 p.m. These data clearly implicate the expectation of food and period of the day with the regulation of insulin action. All these modifications in sensitivity occurred without any change in insulin receptor number or affinity. Melatonin, a secretory product of the pineal gland, induced an increase in cell sensitivity to insulin in adipocytes incubated with the highest hormone concentration (100 nM). We conclude that factors related to feeding training and circadian rhythmicity modulate cell sensitivity to insulin.

Effect of monosodium glutamate treatment during neonatal development on lipogenesis rate and lipoprotein lipase activity in adult rats.

Monosodium glutamate (MSG) has been shown to alter several neuroendocrine functions in neonatally treated rats. To evaluate possible alterations in lipogenesis rate and lipoprotein lipase (LPL) activity, male and female rats were injected during the neonatal period with MSG or saline (controls). In male MSG rats, an increase in lipogenesis of liver and retroperitoneal adipose tissues was observed. Triton WR 1339 (an LPL inhibitor) administration decreased retroperitoneal lipogenesis in these animals. In female rats, MSG-treatment increased lipogenesis only in gonadal and retroperitoneal adipose tissues. No change was observed in hepatic lipogenesis and the Triton administration did not change retroperitoneal lipogenesis. LPL activity was increased in the gonadal and retroperitoneal adipose tissues in male and female MSG-treated rats. These data suggest that there is a specific sex-dependent response in the development of MSG-induced obesity.