RESUMO
Clinical evidence has shown that a high consumption of sugar-sweetened beverages is a risk factor for developing obesity and metabolic syndrome. There has also been increasing interest in the potential effects of high-fructose intake on behavior. The present study evaluated sex differences in behavioral and metabolic characteristics in response to chronic fructose intake in mice. Swiss mice (3-months-old) had access to tap water or fructose-water solution (at 15% or 30% w/v) ad libitum for nine weeks. After the 8 weeks, the mice were submitted to a battery of behavioral tests. A glucose tolerance test was performed one day after these behavioral tests, and the next day blood was collected for biochemical analysis. At a 15% concentration, fructose-intaking resulted in higher plasma cholesterol levels and glucose intolerance in mice that paralleled with a passive stress-coping behavior in the female mice and lower self-care behavior in the male and the female mice. At a 30% concentration, fructose-intaking resulted in higher body mass gain and higher plasma cholesterol and triglycerides levels in the male and the female mice, whereas glucose intolerance was more pronounced in the male mice. Spatial memory impairments and lower self-care behavior were observed in the male and the female mice, while passive stress-coping behavior was observed only in the female mice. Collectively, high-fructose intake induces metabolic and behavioral alterations in mice, with the males being more susceptible to glucose metabolism dysfunctions and the females to depressive-like endophenotypes.
Assuntos
Frutose , Intolerância à Glucose , Animais , Bebidas , Glicemia , Feminino , Intolerância à Glucose/induzido quimicamente , Teste de Tolerância a Glucose , Masculino , Camundongos , ObesidadeRESUMO
Actualmente los edulcorantes no nutritivos (ENN) son ampliamente usados para endulzar los alimentos en reemplazo de los azúcares simples, con la ventaja de no aportar energía. A pesar de que en general no presentan efectos tóxicos, los estudios epidemiológicos no han podido evidenciar que su uso contribuya a mejorar la pérdida de peso, sino por el contrario, han revelado que los ENN pueden inducir alteraciones metabólicas como intolerancia a la glucosa. Estudios in vivo e in vitro han mostrado que muchos ENN activan a receptores del sabor dulce no sólo en los botones gustativos, sino que también en los receptores presentes en tejidos como el adiposo y pancreático, interfiriendo con su función normal. Además, el consumo ENN se ha asociado a alteraciones de la composición de la microbiota intestinal que conducen a una respuesta inflamatoria de bajo grado. La nueva evidencia disponible sobre los ENN hace necesario evaluar el uso cada vez más intenso de los ENN en Chile. Debido a que el gusto exacerbado por el sabor dulce que cultivamos desde la infancia es un potente catalizador del uso de ENN, proponemos que una oportuna educación del sentido del gusto puede contribuir a mejorar las elecciones alimentarias.
Currently, non-nutritive sweeteners (NNS) are widely used to sweeten foods instead of simple sugars, as they possess the advantage of not contributing to energy intake. Although they do not present toxic effects in general, epidemiological studies have not been able to show benefits when they are used in weight loss programs. However, they could induce metabolic alterations such as glucose intolerance. In vivo and in vitro studies have shown that many NNSs activate sweet taste receptors not only in the taste buds, but also in receptors present in adipose and pancreatic tissues, interfering with their normal function. In addition, NNS consumption has been associated with an alteration in the composition of the gut microbiota that leads to a low-grade inflammatory response. Due to the wide use of NNS in Chile, it is necessary to evaluate the potential health effects of using NNS in the Chilean population. We propose that a timely education of the sense of taste can contribute to moderating the preference for higher levels of sweet taste that humans develop in childhood, which could help to improve food choices.
Assuntos
Humanos , Intolerância à Glucose/induzido quimicamente , Adoçantes não Calóricos/efeitos adversos , Chile , Saúde Global , Diabetes Mellitus/induzido quimicamente , ObesidadeRESUMO
BACKGROUND: Limited studies have been carried out with prednisone (PRED) in treatment by glucose intolerant individuals, even in this model the animals presented low blood glucose levels at adulthood, by the high regenerative capacity of ß-cell. OBJECTIVE: The aim was to evaluate the effects of the treatment of PRED in mild diabetes on biochemical and immunological biomarkers. METHODS: Rats were randomly divided into four groups: control (C), treated control C+PRED (treatment of 1.25 mg/Kg/day PRED); diabetic DM (mild diabetes) and treated diabetic DM+PRED (treatment with same dose as C+PRED group). Untreated groups received vehicle, adjusted volume to body weight. The treatment lasted 21 days and measured body weight, food and water intake, and glycemia weekly. In the 3rd week, the Oral Glucose Tolerance Test (OGTT) and the Insulin Tolerance Test (ITT) was performed. On the last day, the rats were killed and the blood was collected for biochemical analyzes, leukogram and immunoglobulin G levels. RESULTS: There was a significant decrease in body weight in mild diabetes; however, the treatment in diabetic groups increased food intake, glycemia, and the number of total leukocytes, lymphocytes and neutrophils. On the other hand, it decreased the levels of triglycerides, high-density and very lowdensity lipoproteins. In addition, diabetic groups showed glucose intolerance and mild insulin resistance, confirming that this model induces glucose intolerant in adult life. CONCLUSION: The results showed that the use of prednisone is not recommended for glucose intolerant individuals and should be replaced in order to not to aggravate this condition.
Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Intolerância à Glucose/sangue , Intolerância à Glucose/induzido quimicamente , Prednisona/uso terapêutico , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Teste de Tolerância a Glucose/métodos , Resistência à Insulina/fisiologia , Prednisona/efeitos adversos , Distribuição Aleatória , Ratos , Resultado do TratamentoRESUMO
Obesity predisposes to glucose intolerance and type 2 diabetes (T2D). This disease is often characterized by insulin resistance, changes in insulin clearance, and ß-cell dysfunction. However, studies indicate that, for T2D development, disruptions in glucagon physiology also occur. Herein, we investigated the involvement of glucagon in impaired glycemia control in monosodium glutamate (MSG)-obese mice. Male Swiss mice were subcutaneously injected daily, during the first 5 days after birth, with MSG (4 mg/g body weight [BW]) or saline (1.25 mg/g BW). At 90 days of age, MSG-obese mice were hyperglycemic, hyperinsulinemic, and hyperglucagonemic and had lost the capacity to increase their insulin/glucagon ratio when transitioning from the fasting to fed state, exacerbating hepatic glucose output. Furthermore, hepatic protein expressions of phosphorylated (p)-protein kinase A (PKA) and cAMP response element-binding protein (pCREB), and of phosphoenolpyruvate carboxykinase (PEPCK) enzyme were higher in fed MSG, before and after glucagon stimulation. Increased pPKA and phosphorylated hormone-sensitive lipase content were also observed in white fat of MSG. MSG islets hypersecreted glucagon in response to 11.1 and 0.5 mmol/L glucose, a phenomenon that persisted in the presence of insulin. Additionally, MSG α cells were hypertrophic displaying increased α-cell mass and immunoreactivity to phosphorylated mammalian target of rapamycin (pmTOR) protein. Therefore, severe glucose intolerance in MSG-obese mice was associated with increased hepatic glucose output, in association with hyperglucagonemia, caused by the refractory actions of glucose and insulin in α cells and via an effect that may be due to enhanced mTOR activation.
Assuntos
Glicemia/metabolismo , Células Secretoras de Glucagon/metabolismo , Glucagon/sangue , Intolerância à Glucose/sangue , Resistência à Insulina , Insulina/sangue , Obesidade/sangue , Glutamato de Sódio , Tecido Adiposo Branco/metabolismo , Animais , Biomarcadores/sangue , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Modelos Animais de Doenças , Intolerância à Glucose/induzido quimicamente , Intolerância à Glucose/fisiopatologia , Fígado/metabolismo , Masculino , Camundongos , Obesidade/induzido quimicamente , Obesidade/fisiopatologia , Fosfoenolpiruvato Carboxiquinase (ATP)/metabolismo , Fosforilação , Serina-Treonina Quinases TOR/metabolismoRESUMO
No presente estudo, avaliamos o impacto da deficiência de vitamina D em camundongos fêmeas ovariectomizadas. A hipótese do nosso estudo é que a deficiência de vitamina D aumenta a inflamação no tecido adiposo e promove acúmulo de gordura hepática em modelo de menopausa. Camundongos C57BL/6 fêmeas, com três meses de idade, foram ovariectomizados ou não, e divididos em grupos controle (C, alimentado com dieta padrão), ovariectomizados (Ovx, alimentado com dieta padrão), controle sem vitamina D (C (D-), alimentado com dieta padrão sem vitamina D) e ovariectomizados sem vitamina D (Ovx (D-), alimentados com dieta padrão sem vitamina D) por doze semanas. Como resultados, no grupo Ovx (D-), houve resistência à insulina e intolerância à glicose, além do aumento da massa corporal. No fígado, houve aumento da esteatose hepática, com consequente aumento da lipogênese e inflamação, fatores que foram comprovados pelo aumento na expressão de genes e proteínas responsáveis pelo metabolismo lipídico. Além disso, houve redução da beta-oxidação de ácidos graxos. No tecido adiposo periovariano, a ovariectomia aumentou a área média dos adipócitos e a expressão proteica e gênica de citocinas pró-inflamatórias. Associado aos achados supracitados, houve aumento do metabolismo local da vitamina D, como forma de compensar a deficiência dessa vitamina. Em conclusão, os achados experimentais atuais são robustos e demonstram que a ovariectomia e a restrição dietética de vitamina D em camundongos têm efeitos adversos aditivos que levam a um aumento da massa corporal, da esteatose hepática e resistência à insulina. Esses achados estão ligados ao aumento dos marcadores de lipogênese e diminuição da beta-oxidação, predispondo ao acúmulo de gordura no fígado, assim como o aumento da inflamação no tecido adiposo periovariano.
In the present study, we have evaluated the impact of vitamin D deficiency in ovariectomized female mice. The hypothesis of our study is that vitamin D deficiency increases the inflammation in adipose tissue and promotes accumulation of hepatic fat in the menopause model. Female C57BL / 6 mice, three months old, were ovariectomized or not, and divided into control (C, fed control diet), ovariectomized (Ovx fed control diet), control without vitamin D (D-), fed control diet without vitamin D) and ovariectomized without vitamin D (Ovx (D-), fed control diet without vitamin D) for twelve weeks. As a result, in Ovx (D-) group there was insulin resistance and glucose intolerance, as well as an increase in body mass. In the liver, there was an increase in hepatic steatosis, with consequent increase in lipogenesis and inflammation due to the increase in the expression of genes and proteins of lipid metabolism. In addition, there was a reduction of beta-oxidation and reduction of fatty acid oxidation. In periovarian adipose tissue, ovariectomy increased the mean area of adipocytes and protein and gene expression of pro-inflammatory cytokines. Associated with the findings, there was increase in the local vitamin D metabolism, to compensate the deficiency of this vitamin. In conclusion, that current experimental findings are robust showing that ovariectomy and vitamin D dietary restriction in mice have additive adverse effects that lead to increased body mass, hepatic steatosis and insulin resistance. These findings are linked to increase of lipogenesis markers and decreased of beta-oxidation, predisposing to accumulation of fat in the liver, as well as increased inflammation in periovarian adipose tissue.
Assuntos
Animais , Cobaias , Camundongos , Deficiência de Vitamina D/induzido quimicamente , Menopausa , Vitamina D , Resistência à Insulina , Ovariectomia , Tecido Adiposo/metabolismo , Intolerância à Glucose/induzido quimicamente , Dieta/métodos , Fígado Gorduroso/metabolismoRESUMO
In this work, we evaluated the effects of Psidium cattleianum (Red Type) (PcRT) fruit extract on metabolic, behavioral, and neurochemical parameters in rats fed with a highly palatable diet (HPD) consisted of sucrose (65% carbohydrates being 34% from condensed milk, 8% from sucrose and 23% from starch, 25% protein and 10% fat). Animals were divided into 4 groups: standard chow, standard chow + PcRT extract (200 mg/Kg/day by gavage), HPD, HPD + extract. The animals were treated for 150 days. Concerning chemical profiling, LC/PDA/MS/MS analysis revealed cyanidin-3-O-glucoside as the only anthocyanin in the PcRT extract. Our results showed that the animals exposed to HPD presented glucose intolerance, increased weight gain and visceral fat, as well as higher serum levels of glucose, triacylglycerol, total cholesterol, LDL-cholesterol and interleukin-6. These alterations were prevented by PcRT. In addition, HPD caused an increase in immobility time in a forced swimming test and the fruit extract prevented this alteration, indicating an antidepressant-like effect. PcRT treatment also prevented increased acetylcholinesterase activity in the prefrontal cortex caused by HPD consumption. Moreover, PcRT extract was able to restore Ca2+-ATPase activity in the prefrontal cortex, hippocampus, and striatum, as well as Na+,K+-ATPase activity in the prefrontal cortex and hippocampus. PcRT treatment decreased thiobarbituric acid-reactive substances, nitrite, and reactive oxygen species levels and prevented the reduction of superoxide dismutase activity in all cerebral structures of the HPD group. Additionally, HPD decreased catalase in the hippocampus and striatum. However, the extract prevented this change in the hippocampus. Our results showed that this berry extract has antihyperglycemic and antihyperlipidemic effects, and neuroprotective properties, proving to be a potential therapeutic agent for individuals with metabolic syndrome.
Assuntos
Antocianinas/farmacologia , Antioxidantes/farmacologia , Glucosídeos/farmacologia , Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Síndrome Metabólica/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Psidium/química , Animais , Antocianinas/química , Antidepressivos/química , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Antioxidantes/química , Comportamento Animal/efeitos dos fármacos , Brasil , Catalase/metabolismo , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Dieta da Carga de Carboidratos/efeitos adversos , Modelos Animais de Doenças , Intolerância à Glucose/induzido quimicamente , Intolerância à Glucose/tratamento farmacológico , Intolerância à Glucose/metabolismo , Glucosídeos/química , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipoglicemiantes/química , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/química , Hipolipemiantes/uso terapêutico , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/metabolismo , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Espectrometria de Massas em Tandem , Aumento de Peso/efeitos dos fármacosRESUMO
The aim of this study was to investigate the effect of Eugenia uniflora fruit (red type) extract on metabolic status, as well as on neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD). Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. Our data showed that HPD caused glucose intolerance, increased visceral fat, weight gain, as well as serum glucose, triacylglycerol, total cholesterol and LDL cholesterol; however, E. uniflora prevented these alterations. The extract decreased lipid peroxidation and prevented the reduction of superoxide dismutase and catalase activities in the prefrontal cortex, hippocampus and striatum of animals submitted to HPD. We observed a HPD-induced reduction of thiol content in these cerebral structures. The extract prevented increased acetylcholinesterase activity in the prefrontal cortex caused by HPD and the increase in immobility time observed in the forced swim test. Regarding chemical composition, LC/MS analysis showed the presence of nine anthocyanins as the major compounds. In conclusion, E. uniflora extract showed benefits against metabolic alterations caused by HPD, as well as exhibited antioxidant and antidepressant-like effects.
Assuntos
Antidepressivos/farmacologia , Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Depressão/prevenção & controle , Eugenia/química , Frutas/química , Síndrome Metabólica/prevenção & controle , Extratos Vegetais/farmacologia , Acetilcolinesterase/metabolismo , Adiposidade/efeitos dos fármacos , Animais , Antidepressivos/isolamento & purificação , Antidepressivos/normas , Antioxidantes/isolamento & purificação , Antioxidantes/normas , Comportamento Animal/efeitos dos fármacos , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Catalase/metabolismo , Depressão/sangue , Depressão/fisiopatologia , Depressão/psicologia , Dieta Hiperlipídica , Sacarose Alimentar , Modelos Animais de Doenças , Dislipidemias/sangue , Dislipidemias/induzido quimicamente , Dislipidemias/prevenção & controle , Proteínas Ligadas por GPI/metabolismo , Intolerância à Glucose/sangue , Intolerância à Glucose/induzido quimicamente , Intolerância à Glucose/prevenção & controle , Peroxidação de Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/fisiopatologia , Atividade Motora/efeitos dos fármacos , Obesidade/sangue , Obesidade/induzido quimicamente , Obesidade/prevenção & controle , Fitoterapia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/normas , Plantas Medicinais , Ratos Wistar , Superóxido Dismutase/metabolismo , Fatores de Tempo , Aumento de Peso/efeitos dos fármacosRESUMO
Exposure to fine particulate matter (PM2.5) air pollution is a risk factor for type 2 diabetes (T2DM). We argue whether the potentiating effect of PM2.5 over the development of T2DM in high-fat diet (HFD)-fed mice would be related to modification in cell stress response, particularly in antioxidant defenses and 70-kDa heat shock proteins (HSP70) status. Male mice were fed standard chow or HFD for 12 weeks and then randomly exposed to daily nasotropic instillation of PM2.5 for additional 12 weeks under the same diet schedule, divided into four groups (n = 14-15 each): Control, PM2.5, HFD, and HFD + PM2.5 were evaluated biometric and metabolic profiles of mice, and cellular stress response (antioxidant defense and HSP70 status) of metabolic tissues. Extracellular to intracellular HSP70 ratio ([eHSP72]/[iHSP70]), viz. H-index, was then calculated. HFD + PM2.5 mice presented a positive correlation between adiposity, increased body weight and glucose intolerance, and increased glucose and triacylglycerol plasma levels. Pancreas exhibited lower iHSP70 expression, accompanied by 3.7-fold increase in the plasma to pancreas [eHSP72]/[iHSP70] ratio. Exposure to PM2.5 markedly potentiated metabolic dysfunction in HFD-treated mice and promoted relevant alteration in cell stress response assessed by [eHSP72]/[iHSP70], a relevant biomarker of chronic low-grade inflammatory state and T2DM risk.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Intolerância à Glucose/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP72/metabolismo , Obesidade/metabolismo , Material Particulado/toxicidade , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/patologia , Administração Intranasal , Animais , Biomarcadores/metabolismo , Catalase/genética , Catalase/metabolismo , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica/efeitos adversos , Regulação da Expressão Gênica , Intolerância à Glucose/induzido quimicamente , Intolerância à Glucose/genética , Intolerância à Glucose/patologia , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP72/genética , Resistência à Insulina , Masculino , Camundongos , Obesidade/induzido quimicamente , Obesidade/genética , Obesidade/patologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Aumento de Peso/efeitos dos fármacosRESUMO
We aimed to evaluate the effects of aerobic exercise training (4 days) and metformin exposure on acute glucose intolerance after dexamethasone treatment in rats. Forty-two adult male Wistar rats (8 weeks old) were divided randomly into four groups: sedentary control (SCT), sedentary dexamethasone-treated (SDX), training dexamethasone-treated (DPE), and dexamethasone and metformin treated group (DMT). Glucose tolerance tests and in situ liver perfusion were undertaken on fasting rats to obtain glucose profiles. The DPE group displayed a significant decrease in glucose values compared with the SDX group. Average glucose levels in the DPE group did not differ from those of the DMT group, so we suggest that exercise training corrects dexamethasone-induced glucose intolerance and improves glucose profiles in a similar manner to that observed with metformin. These data suggest that exercise may prevent the development of glucose intolerance induced by dexamethasone in rats to a similar magnitude to that observed after metformin treatment.
Assuntos
Animais , Masculino , Intolerância à Glucose/prevenção & controle , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Condicionamento Físico Animal/fisiologia , Glicemia/análise , Dexametasona/farmacologia , Jejum/sangue , Teste de Tolerância a Glucose , Glucocorticoides/farmacologia , Intolerância à Glucose/induzido quimicamente , Glucose/análise , Hiperglicemia/terapia , Fígado/química , Perfusão , Distribuição Aleatória , Ratos Wistar , NataçãoRESUMO
We aimed to evaluate the effects of aerobic exercise training (4 days) and metformin exposure on acute glucose intolerance after dexamethasone treatment in rats. Forty-two adult male Wistar rats (8 weeks old) were divided randomly into four groups: sedentary control (SCT), sedentary dexamethasone-treated (SDX), training dexamethasone-treated (DPE), and dexamethasone and metformin treated group (DMT). Glucose tolerance tests and in situ liver perfusion were undertaken on fasting rats to obtain glucose profiles. The DPE group displayed a significant decrease in glucose values compared with the SDX group. Average glucose levels in the DPE group did not differ from those of the DMT group, so we suggest that exercise training corrects dexamethasone-induced glucose intolerance and improves glucose profiles in a similar manner to that observed with metformin. These data suggest that exercise may prevent the development of glucose intolerance induced by dexamethasone in rats to a similar magnitude to that observed after metformin treatment.
Assuntos
Intolerância à Glucose/prevenção & controle , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Condicionamento Físico Animal/fisiologia , Animais , Glicemia/análise , Dexametasona/farmacologia , Jejum/sangue , Glucocorticoides/farmacologia , Glucose/análise , Intolerância à Glucose/induzido quimicamente , Teste de Tolerância a Glucose , Hiperglicemia/terapia , Fígado/química , Masculino , Perfusão , Distribuição Aleatória , Ratos Wistar , NataçãoRESUMO
The disruption to glucose homeostasis upon glucocorticoid (GC) treatment in adult male rats has not been fully characterized in older rats or in females. Thus, we evaluated the age- and gender-related changes in glucose homeostasis in GC-treated rats. We injected male and female rats at 3 months and 12 months of age with either dexamethasone (1.0 mg/kg body mass, intraperitoneally) or saline, daily for 5 days. All of the GC-treated rats had decreased body mass and food intake, and adrenal hypotrophy. Increased glycemia was observed in all of the GC-treated groups and only the 3-month-old female rats were not glucose intolerant. Dexamethasone treatment resulted in hyperinsulinemia and hypertriacylglyceridemia in all of the GC-treated rats. The glucose-stimulated insulin secretion (GSIS) was higher in all of the dexamethasone-treated animals, but it was less pronounced in the older animals. The ß-cell mass was increased in the younger male rats treated with dexamethasone. We conclude that dexamethasone treatment induces glucose intolerance in both the 3- and 12-month-old male rats as well as hyperinsulinemia and augmented GSIS. Three-month-old female rats are protected from glucose intolerance caused by GC, whereas 12-month-old female rats developed the same complications that were present in 3- and 12-month-old male rats.
Assuntos
Anti-Inflamatórios/efeitos adversos , Glucocorticoides/efeitos adversos , Glucose/metabolismo , Imunossupressores/efeitos adversos , Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/patologia , Fatores Etários , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Dexametasona/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Intolerância à Glucose/induzido quimicamente , Homeostase , Hiperinsulinismo/induzido quimicamente , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/patologia , Fígado/metabolismo , Masculino , Ratos Wistar , Fatores Sexuais , Triglicerídeos/sangueRESUMO
Consumption of high levels of fructose in humans and animals leads to metabolic and cardiovascular dysfunction. There are questions as to the role of the autonomic changes in the time course of fructose-induced dysfunction. C57/BL male mice were given tap water or fructose water (100 g/l) to drink for up to 2 mo. Groups were control (C), 15-day fructose (F15), and 60-day fructose (F60). Light-dark patterns of arterial pressure (AP) and heart rate (HR), and their respective variabilities were measured. Plasma glucose, lipids, insulin, leptin, resistin, adiponectin, and glucose tolerance were quantified. Fructose increased systolic AP (SAP) at 15 and 60 days during both light (F15: 123 ± 2 and F60: 118 ± 2 mmHg) and dark periods (F15: 136 ± 4 and F60: 136 ± 5 mmHg) compared with controls (light: 111 ± 2 and dark: 117 ± 2 mmHg). SAP variance (VAR) and the low-frequency component (LF) were increased in F15 (>60% and >80%) and F60 (>170% and >140%) compared with C. Cardiac sympatho-vagal balance was enhanced, while baroreflex function was attenuated in fructose groups. Metabolic parameters were unchanged in F15. However, F60 showed significant increases in plasma glucose (26%), cholesterol (44%), triglycerides (22%), insulin (95%), and leptin (63%), as well as glucose intolerance. LF of SAP was positively correlated with SAP. Plasma leptin was correlated with triglycerides, insulin, and glucose tolerance. Results show that increased sympathetic modulation of vessels and heart preceded metabolic dysfunction in fructose-consuming mice. Data suggest that changes in autonomic modulation may be an initiating mechanism underlying the cluster of symptoms associated with cardiometabolic disease.
Assuntos
Frutose/efeitos adversos , Intolerância à Glucose/metabolismo , Sistema Nervoso Simpático/fisiopatologia , Animais , Barorreflexo/efeitos dos fármacos , Barorreflexo/fisiologia , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Modelos Animais de Doenças , Intolerância à Glucose/induzido quimicamente , Intolerância à Glucose/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Insulina/sangue , Resistência à Insulina/fisiologia , Leptina/sangue , Lipídeos/sangue , Masculino , Camundongos , Sistema Nervoso Simpático/metabolismoRESUMO
AIM: Glucocorticoid administration induces insulin resistance (IR) and enhances islet mass and insulin secretion in rodents and humans. Here, we analysed whether these effects are still present after the interruption of dexamethasone treatment. METHODS: Adult Wistar rats were distributed into CTL (daily injection of saline for five consecutive days), DEX (daily injection of 1 mg kg(-1) body wt of dexamethasone for five consecutive days) and DEX(10) (5 days of dexamethasone treatment, followed by a period of 10 days without dexamethasone). RESULTS: In vivo experiments indicated that the marked hyperinsulinemia found in DEX rats during fasting and fed states was normalized in the DEX(10) group. Furthermore, the IR and glucose intolerance observed in DEX were restored in DEX(10) rats. Islets from DEX rats secreted more insulin in response to increasing concentrations of glucose and other metabolic and non-metabolic stimuli, compared with that in the CTL group. The insulin secretion for the most compounds studied returned to CTL values in DEX(10) islets. Increased insulin secretion correlated well with the augmentation in ß-cell proliferation and mass in DEX rats, and these morphological alterations were normalized in islets from DEX(10) rats. In parallel, the increased levels of proteins involved in ß-cell proliferation such as Cd2 and Cdk4 observed in DEX islets were also normalized in DEX(10) islets. CONCLUSION: These data strongly support the view that almost all the morphophysiological alterations induced by dexamethasone in the endocrine pancreas are reverted after discontinuation of the treatment. This information is important, considering the frequent use of glucocorticoids in humans.
Assuntos
Dexametasona/análogos & derivados , Glucocorticoides/administração & dosagem , Insulina/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Adaptação Fisiológica , Animais , Glicemia/metabolismo , Proteínas de Ciclo Celular/metabolismo , Morte Celular , Proliferação de Células , Dexametasona/administração & dosagem , Dexametasona/toxicidade , Esquema de Medicação , Glucocorticoides/toxicidade , Intolerância à Glucose/induzido quimicamente , Intolerância à Glucose/metabolismo , Hiperinsulinismo/induzido quimicamente , Hiperinsulinismo/metabolismo , Insulina/sangue , Resistência à Insulina , Secreção de Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Masculino , Ratos , Ratos Wistar , Fatores de TempoRESUMO
The metabolic syndrome (MS) has been associated with hyperactivity of the renin-angiotensin-aldosterone system (RAAS). To assess the hypothesis that diuretic therapy in MS patients through further stimulation of RAAS would elicit greater potassium (K) depletion, two groups of hypertensive patients with (MS group [MSG]; n=20) and without (control group [CG]; n=19) MS were studied. Plasma renin activity (PRA), aldosterone (PA), and K levels were determined and an oral glucose tolerance test with plasma insulin determinations for calculation of homeostasis model assessment of insulin resistance (HOMA-IR), sensitivity (ISI), and secretion (HOMA-beta) was performed, both before and 12 weeks after hydrochlorothiazide (HCT; 25 mg/d) therapy. At baseline, higher HOMA IR and HOMA-beta and lower ISI and plasma K were found in the MSG than in the CG, with no differences in PA and PRA between groups. With therapy, PRA increased similarly in both groups while PA increased only in the MSG. However, greater reduction in plasma K occurred in the CG, and the 2 groups reached similar final K values. Impairment in glucose tolerance occurred in both groups, with no change in HOMA-beta in the CG and reduction in the MSG, suggesting that diuretic therapy increases insulin resistance and impairs insulin secretion independent of abdominal obesity. These alterations could not be attributed to hyperactivity of RAAS.
Assuntos
Intolerância à Glucose/induzido quimicamente , Hipertensão/fisiopatologia , Síndrome Metabólica/fisiopatologia , Deficiência de Potássio/induzido quimicamente , Sistema Renina-Angiotensina/fisiologia , Inibidores de Simportadores de Cloreto de Sódio/efeitos adversos , Adulto , Glicemia/metabolismo , Pressão Sanguínea/fisiologia , Estudos de Casos e Controles , Feminino , Intolerância à Glucose/sangue , Intolerância à Glucose/fisiopatologia , Humanos , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Resistência à Insulina/fisiologia , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Potássio/sangue , Deficiência de Potássio/sangue , Deficiência de Potássio/fisiopatologia , Estudos Prospectivos , Inibidores de Simportadores de Cloreto de Sódio/uso terapêuticoRESUMO
AIM OF THE STUDY: To evaluate the glucose metabolism in acromegalic patients before and after treatment with octreotide LAR. PATIENTS AND METHODS: This was a prospective and longitudinal study involving 30 patients from the acromegaly research outpatient clinic of the Endocrinology unit of the HUCFF/UFRJ. They underwent clinical and laboratorial evaluations, with measurements of growth hormone (GH), insulin-like growth factor type I (IGF-I), insulin, proinsulin, C peptide, glycosylated hemoglobin (HbA1c), IGF binding protein type 1 (IGFBP-1) and glucose, during oral glucose tolerance test (OGTT), before and after six months of treatment with octreotide LAR. The Wilcoxon signed-rank test was used and values of 5% were considered statistically significant. RESULTS: We found 16 (54%) patients with normal glucose tolerance, 7 (23%) with impaired glucose tolerance and 7 (23%) diabetics. Twelve patients completed the six-month treatment, out of which three showed worsening of glucose tolerance and two (diabetics) had worse blood glucose control. Whereas there was an increase in waist circumference (p=0.03), there was a decrease in GH (p=0.04), with %IGF-I above the upper limit of reference values (% ULRV) [p=0.001], insulin (p=0.019), C peptide levels (p=0.002) and homeostatic model assessment (HOMA-IR) [p=0.039]. CONCLUSIONS: In this series, treatment with octreotide LAR led to a worsening of glucose tolerance in three non-diabetic patients and worsened glycemic control in two diabetics, in spite of reducing insulin resistance.
Assuntos
Acromegalia/metabolismo , Antineoplásicos Hormonais/uso terapêutico , Intolerância à Glucose/diagnóstico , Glucose/metabolismo , Hormônio do Crescimento Humano/sangue , Octreotida/uso terapêutico , Acromegalia/tratamento farmacológico , Adolescente , Antineoplásicos Hormonais/efeitos adversos , Biomarcadores/sangue , Feminino , Intolerância à Glucose/induzido quimicamente , Teste de Tolerância a Glucose , Hormônio do Crescimento Humano/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Octreotida/efeitos adversos , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
OBJETIVO: Avaliar o metabolismo da glicose em pacientes acromegálicos antes e após o tratamento com octreotide LAR. PACIENTES E MÉTODOS: Este foi um estudo longitudinal e prospectivo com 30 pacientes do ambulatório de pesquisa em acromegalia do Serviço de Endocrinologia do Hospital Universitário Clementino Fraga Filho da Universidade Federal do Rio de Janeiro (HUCFF/UFRJ). Eles foram submetidos à avaliação clínica e laboratorial com dosagens de hormônio do crescimento (GH), fator de crescimento semelhante à insulina tipo I (IGF-I), insulina, pró-insulina, peptídeo C, hemoglobina glicosilada (HbA1c), proteína de ligação do IGF tipo 1 (IGFBP-1) e a um teste oral de tolerância à glicose (TOTG), antes e após seis meses de tratamento com octreotide LAR. Foi aplicado o teste dos postos sinalizados de Wilcoxon e o critério de determinação de significância adotado foi o nível de 5 por cento. RESULTADOS: Encontraram-se 16 pacientes (54 por cento) com tolerância normal à glicose, sete (23 por cento) com intolerância à glicose e sete (23 por cento) com diabetes melito (DM). Doze pacientes completaram os seis meses de tratamento, sendo que houve piora da tolerância à glicose em três e piora do controle glicêmico dos dois pacientes diabéticos. Houve aumento da circunferência abdominal (p = 0,03) e queda do GH (p = 0,04), por cento IGF-I acima do limite superior do valor de referência ( por centoLSVR) (p = 0,001), insulina (p = 0,019), peptídeo C (p = 0,002) e do modelo de avaliação homeostática (HOMA-IR) (p = 0,039). CONCLUSÕES: Nesta série, o tratamento com octreotide LAR acarretou piora da tolerância à glicose em três pacientes não-diabéticos e piora do controle glicêmico em dois diabéticos, apesar da diminuição da resistência insulínica (RI).
AIM OF THE STUDY: To evaluate the glucose metabolism in acromegalic patients before and after treatment with octreotide LAR. PATIENTS AND METHODS: This was a prospective and longitudinal study involving 30 patients from the acromegaly research outpatient clinic of the Endocrinology unit of the HUCFF/UFRJ. They underwent clinical and laboratorial evaluations, with measurements of growth hormone (GH), insulin-like growth factor type I (IGF-I), insulin, proinsulin, C peptide, glycosylated hemoglobin (HbA1c), IGF binding protein type 1 (IGFBP-1) and glucose, during oral glucose tolerance test (OGTT), before and after six months of treatment with octreotide LAR. The Wilcoxon signed-rank test was used and values of 5 percent were considered statistically significant. RESULTS: We found 16 (54 percent) patients with normal glucose tolerance, 7 (23 percent) with impaired glucose tolerance and 7 (23 percent) diabetics. Twelve patients completed the six-month treatment, out of which three showed worsening of glucose tolerance and two (diabetics) had worse blood glucose control. Whereas there was an increase in waist circumference (p=0.03), there was a decrease in GH (p=0.04), with percentIGF-I above the upper limit of reference values ( percent ULRV) [p=0.001], insulin (p=0.019), C peptide levels (p=0.002) and homeostatic model assessment (HOMA-IR) [p=0.039]. CONCLUSIONS: In this series, treatment with octreotide LAR led to a worsening of glucose tolerance in three non-diabetic patients and worsened glycemic control in two diabetics, in spite of reducing insulin resistance.
Assuntos
Adolescente , Feminino , Humanos , Masculino , Adulto Jovem , Acromegalia/metabolismo , Antineoplásicos Hormonais/uso terapêutico , Intolerância à Glucose/diagnóstico , Glucose/metabolismo , Hormônio do Crescimento Humano/sangue , Octreotida/uso terapêutico , Acromegalia/tratamento farmacológico , Antineoplásicos Hormonais/efeitos adversos , Biomarcadores/sangue , Teste de Tolerância a Glucose , Intolerância à Glucose/induzido quimicamente , Hormônio do Crescimento Humano , Fator de Crescimento Insulin-Like I/metabolismo , Octreotida/efeitos adversos , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To determine the prevalence of secondary effects on lipid metabolism as a result of highly active antiretroviral therapy (HAART), as well as the impact of different types of antiretroviral regimens on lipids and glucose in a group of patients in Yucatan, Mexico. MATERIAL AND METHODS: A cross-sectional study was conducted. A questionnaire created for this study was administered to each patient and total cholesterol, triglycerides and fasting glucose values were determined. The presence of hyperlipidemia and alterations in glucose were determined as well as their relation to the epidemiological variables obtained from the questionnaire. RESULTS: A total of 211 subjects were studied [36 (17%) of which were women and 175 (83%) men]. Ninety-two patients (44%) were found to have hyperlipidemia. Of these, 43 (20%) had hypercholesterolemia (HC) and 82 (39%) hypertriglyceridaemia (HT). The presence of combined HC and HT was observed in 30 (14%) patients. Nineteen (9%) patients had alterations in glucose, six (3%) diabetes mellitus and 13 (6%) impaired glucose tolerance. The variables associated with the presence of hyperlipidemia were: levels of lymphocytes CD4 >350 cells/microl (OR = 2.79 1.08-7.27, p = 0.03), male gender (OR = 3.6 1.4-9.12, p = 0.006) and the use of nucleoside-reverse transcriptase inhibitors (NRTI) (OR = 3.1 1.2-8.1, p = 0.01). CONCLUSIONS: Patients with HIV infection who receive HAART have an increased risk of presenting hyperlipidemia. In this group of patients the presence of hyperlipidemia and impaired glucose tolerance was significant. Unlike what has been indicated in most published reports, the alterations of lipids were associated more frequently with INTR use, for which it is concluded that the pathogeny of these alterations is not unique, that it is probable that concurrent effects exist between different antiretroviral drug families and that other host factors are involved in the pathogenic mechanism of these alterations.
Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Antivirais/efeitos adversos , Intolerância à Glucose/induzido quimicamente , Intolerância à Glucose/epidemiologia , Infecções por HIV/tratamento farmacológico , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/epidemiologia , Adulto , Idoso , Antivirais/uso terapêutico , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
OBJETIVO: Determinar la prevalencia de los efectos secundarios sobre el metabolismo de los lípidos y la glucosa provocados por la terapia antirretrovírica hiperactiva (TARHA), así como el impacto que el uso de los distintos esquemas de antirretrovíricos tiene sobre los lípidos y la glucosa en un grupo de pacientes de Yucatán, México.MATERIAL Y MÉTODOS: Se realizó un estudio transversal. A cada paciente se le aplicó un cuestionario creado para este estudio y se le determinaron los valores de colesterol total, triglicéridos y glucosa en ayuno. Se determinó la prevalencia de hiperlipidemia y alteraciones de la glucosa y su relación con las variables de la encuesta.RESULTADOS: Se estudiaron 211 pacientes, 36 (17%) mujeres y 175 (83%) hombres; 92 (44%) tuvieron hiperlipidemia. De éstos, 43 (20%) presentaron hipercolesterolemia (HC) y 82 (39%) hipertrigliceridemia (HT). La presencia de HC e HT combinadas se verificó en 30 (14%) pacientes; además, 19 (9%) pacientes exhibieron alteraciones en la glucosa, seis (3%) presentaron diabetes mellitus y 13 (6%), intolerancia a la glucosa. Las variables que se vincularon con la presencia de hiperlipidemia fueron los números de linfocitos CD4 >350 células/µl [RM= 2.79 (1.08-7.27), p= 0.03], el género masculino [RM= 3.6 (1.4-9.12), p= 0.006] y el uso de nucleósidos inhibidores de la transcriptasa inversa (NITI) [RM= 3.1 (1.2-8.1), p= 0.01].CONCLUSIONES: Los pacientes con la infección por el VIH que reciben terapia antirretroviral (TAR) tienen un riesgo aumentado de presentar dislipidemia. A diferencia de lo que informan la mayor parte las publicaciones, las alteraciones de los lípidos se asociaron con más frecuencia al uso de NITI, por lo que se concluye que la patogenia de estas alteraciones no es única y que resulta probable la existencia de un efecto sinérgico entre las distintas familias de fármacos antirretrovíricos y que otros factores del huésped participen en la génesis de estas alteraciones.
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Antivirais/efeitos adversos , Intolerância à Glucose/induzido quimicamente , Intolerância à Glucose/epidemiologia , Infecções por HIV/tratamento farmacológico , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/epidemiologia , Antivirais/uso terapêutico , Estudos Transversais , PrevalênciaRESUMO
OBJECTIVE: Recombinant human growth hormone (rhGH) has been used to improve the growth retardation associated with chronic renal insufficiency (CRI) and end-stage renal disease. We determined the incidence of one of four targeted adverse events (AEs): malignancy, slipped capital femoral epiphysis (SCFE), avascular necrosis (AN), and intracranial hypertension (ICH). STUDY DESIGN: During a 6.5-year period, we prospectively assessed patients enrolled in the CRI, dialysis, and transplant registries of the North American Renal Transplant Cooperative Study. The availability of an untreated control population facilitated determining whether or not there was the association between the AE and rhGH treatment. RESULTS: Of the targeted AE, the only significant relation with rhGH treatment was the presence of ICH in patients with CRI; however, in all 3 instances, ICH occurred 2, 50, and 1131 days after discontinuation of rhGH. Considering that the mechanism of ICH in rhGH-treated patients is thought to be increased CSF production, rhGH probably had no role in the development of ICH in at least 2 of the 3 patients with CRI. A number of nontargeted AE were identified that have been associated with rhGH treatment in patients without renal disease. The incidence of glucose intolerance, pancreatitis, progressive deterioration of renal function, acute allograft rejection, and fluid retention were not more frequent in those receiving rhGH treatment compared with the control population. CONCLUSIONS: This report validates the importance of a control population in ascribing AE to any therapeutic intervention. Previously identified AE associated with rhGH treatment are infrequent in patients with CRI and end-stage renal disease.