RESUMO
The cephalic phase of digestion (CPD) has been extensively investigated in terms of digestion and metabolism. Nevertheless, microcirculatory changes required to prepare peripheral tissues in order to dispose nutrients have never been assessed. In this study, microvascular function has been evaluated to determine its behavior and potential association to hormonal secretions during CPD. Thirty-nine healthy male subjects, 23.4 ± 0.5 years (mean ± SD) and BMI of 23.3 ± 2.3 kg/m(2), were randomized into receiving cognitive-sensorial stimuli to elicit CPD (CPD group, n=20) or not (control group, n=19), after a 12-h overnight fast. Main outcomes were differences in resting and peak functional capillary density (FCD, cap/mm(2)); resting red blood cell velocity (RBCV), peak RBCV (RBCV(max)) and time taken to reach it (TRBCV(max)); peak flow and vasomotion, before and after CPD and their associations with insulin and/or pancreatic polypeptide (PP). In the CPD group, basal FCD (24.9 ± 7.6 to 28.3 ± 8.1, p=0.005), peak FCD (27.8 ± 6.3 to 32.6 ± 7.1, p=0.002), RBCV (0.306 ± 0.031 to 0.330 ± 0.027 mm/s, p=0.005), RBCV(max) (0.336 ± 0.029 to 0.398 ± 0.292 mm/s, p=0.005) and peak flow (23.5 ± 14.3 to 26.9 ± 15.8 PU, p<0.01) increased while TRBCV(max) decreased (4.9 ± 1.5 to 3.5 ± 1.2s, p=0.01). No significant changes could be detected in the control group. Groups have not presented differences for insulin, but PP significantly increased in the CPD group and was positively associated to basal FCD increase (rho=0.527, p=0.03). In conclusion, neurally-mediated anticipatory responses of digestion elicited functional capillary recruitment associated to PP in healthy men, suggesting a precocious role for microcirculation in the physiology of digestion and nutrient homeostasis.
Assuntos
Digestão/fisiologia , Microcirculação/fisiologia , Administração Cutânea , Adolescente , Adulto , Velocidade do Fluxo Sanguíneo/fisiologia , Sinais (Psicologia) , Humanos , Insulina/administração & dosagem , Insulina/sangue , Iontoforese/métodos , Masculino , Polipeptídeo Pancreático/sangue , Estimulação Luminosa/métodos , Pele/irrigação sanguínea , Fenômenos Fisiológicos da PeleRESUMO
Increased intestinal permeability is a likely cause of various pathologies, such as allergies and metabolic or even cardiovascular disturbances. Intestinal permeability is found in many severe clinical situations and in common disorders such as irritable bowel syndrome. In these conditions, substances that are normally unable to cross the epithelial barrier gain access to the systemic circulation. To illustrate the potential harmfulness of leaky gut, we present an argument based on examples linked to protein or lipid glycation induced by modern food processing. Increased intestinal permeability should be largely improved by dietary addition of compounds, such as glutamine or curcumin, which both have the mechanistic potential to inhibit the inflammation and oxidative stress linked to tight junction opening. This brief review aims to increase physician awareness of this common, albeit largely unrecognized, pathology, which may be easily prevented or improved by means of simple nutritional changes.
Assuntos
Dieta/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Manipulação de Alimentos , Hipersensibilidade Alimentar/etiologia , Motilidade Gastrointestinal/fisiologia , Absorção Intestinal/fisiologia , Curcumina/uso terapêutico , Glutamina/uso terapêutico , Produtos Finais de Glicação Avançada/efeitos adversos , Produtos Finais de Glicação Avançada/farmacocinética , Humanos , Inflamação/metabolismo , Síndrome Metabólica/etiologia , PermeabilidadeRESUMO
The present review updates the current knowledge on the question of whether high fructose consumption is harmful or not and details new findings which further pushes this old debate. Due to large differences in its metabolic handling when compared to glucose, fructose was indeed suggested to be beneficial for the diet of diabetic patients. However its growing industrial use as a sweetener, especially in soft drinks, has focused attention on its potential harmfulness, possibly leading to dyslipidemia, obesity, insulin resistance/metabolic syndrome and even diabetes. Many new data have been generated over the last years, confirming the lipogenic effect of fructose as well as risks of vascular dysfunction and hypertension. Fructose exerts various direct effects in the liver, affecting both hepatocytes and Kupffer cells and resulting in non-alcoholic steatotic hepatitis, a well known precursor of the metabolic syndrome. Hepatic metabolic abnormalities underlie indirect peripheral metabolic and vascular disturbances, for which uric acid is possibly the culprit.Nevertheless major caveats exist (species, gender, source of fructose, study protocols) which are detailed in this review and presently prevent any firm conclusion. New studies taking into account these confounding factors should be undertaken in order to ascertain whether or not high fructose diet is harmful.
Assuntos
Dieta , Frutose/efeitos adversos , Síndrome Metabólica/induzido quimicamente , Edulcorantes/efeitos adversos , Doenças Vasculares/induzido quimicamente , Frutose/metabolismo , Humanos , Hipertrigliceridemia/induzido quimicamente , Fígado/metabolismo , Fatores de Risco , Edulcorantes/metabolismo , Ácido Úrico/metabolismoRESUMO
Increased intestinal permeability is a likely cause of various pathologies, such as allergies and metabolic or even cardiovascular disturbances. Intestinal permeability is found in many severe clinical situations and in common disorders such as irritable bowel syndrome. In these conditions, substances that are normally unable to cross the epithelial barrier gain access to the systemic circulation. To illustrate the potential harmfulness of leaky gut, we present an argument based on examples linked to protein or lipid glycation induced by modern food processing. Increased intestinal permeability should be largely improved by dietary addition of compounds, such as glutamine or curcumin, which both have the mechanistic potential to inhibit the inflammation and oxidative stress linked to tight junction opening. This brief review aims to increase physician awareness of this common, albeit largely unrecognized, pathology, which may be easily prevented or improved by means of simple nutritional changes.
Assuntos
Humanos , Dieta/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Manipulação de Alimentos , Hipersensibilidade Alimentar/etiologia , Motilidade Gastrointestinal/fisiologia , Absorção Intestinal/fisiologia , Curcumina/uso terapêutico , Glutamina/uso terapêutico , /efeitos adversos , /farmacocinética , Inflamação/metabolismo , Síndrome Metabólica/etiologia , PermeabilidadeRESUMO
The present review updates the current knowledge on the question of whether high fructose consumption is harmful or not and details new findings which further pushes this old debate. Due to large differences in its metabolic handling when compared to glucose, fructose was indeed suggested to be beneficial for the diet of diabetic patients. However its growing industrial use as a sweetener, especially in soft drinks, has focused attention on its potential harmfulness, possibly leading to dyslipidemia, obesity, insulin resistance/metabolic syndrome and even diabetes. Many new data have been generated over the last years, confirming the lipogenic effect of fructose as well as risks of vascular dysfunction and hypertension. Fructose exerts various direct effects in the liver, affecting both hepatocytes and Kupffer cells and resulting in non-alcoholic steatotic hepatitis, a well known precursor of the metabolic syndrome. Hepatic metabolic abnormalities underlie indirect peripheral metabolic and vascular disturbances, for which uric acid is possibly the culprit. Nevertheless major caveats exist (species, gender, source of fructose, study protocols) which are detailed in this review and presently prevent any firm conclusion. New studies taking into account these confounding factors should be undertaken in order to ascertain whether or not high fructose diet is harmful.
Assuntos
Humanos , Dieta , Frutose/efeitos adversos , Síndrome Metabólica/induzido quimicamente , Edulcorantes/efeitos adversos , Doenças Vasculares/induzido quimicamente , Frutose/metabolismo , Hipertrigliceridemia/induzido quimicamente , Fígado/metabolismo , Fatores de Risco , Edulcorantes/metabolismo , Ácido Úrico/metabolismoRESUMO
OBJECTIVE: To study if metformin, when administered to first-degree relatives of type 2 diabetes mellitus subjects who have metabolic syndrome and normal glucose tolerance, could improve the cardiovascular risk profile and reduce the levels of both C-reactive protein and fibrinogen. INTRODUCTION: Metabolic syndrome is associated with higher cardiovascular morbidity and mortality. Metformin has vasculo-protective effects even in normoglycemic subjects, and C-reactive protein and fibrinogen are considered markers of endothelial injury and inflammation. METHODS: Thirty-one non-diabetic first-degree relatives of type 2 diabetes mellitus subjects with metabolic syndrome were randomized (1:1) and double-blinded for placement in the placebo and metformin groups (850 mg bid/+/-90 days); 16 subjects were administered metformin (mean age 40.0 [33.5-50] years; 13 females) and 15 subjects were in the placebo group (mean age 37.0 [32-42] years; 9 females). Blood samples were collected at baseline and at the end of treatment for biochemical analyses, including an assessment of C-reactive protein and fibrinogen levels. RESULTS: Metformin improved the lipid profile and decreased fasting plasma glucose, systolic blood pressure, weight and body mass index without changing body composition. For those in the placebo we identified no changes in fibrinogen (282.2 [220.4-323.7] mg/L vs. 286.7 [249.6-295.1] mg/L; NS) or in C-reactive protein levels (0.68 [0.3-1.2] vs. 0.64 [0.3-1.0] mg/L; NS). The same was also observed for the levels of fibrinogen (303.9 [217.6-347.6] mg/L vs. 290.9 [251.5-301.9] mg/L; NS) and C-reactive proteins (0.78 [0.3-1.1] vs. 0.80 [0.4-0.9] mg/L; NS) in the metformin group. CONCLUSIONS: Metformin treatment in first-degree relatives of type 2 diabetes mellitus sufferers who have metabolic syndrome and normal glucose tolerance improved the cardiovascular risk profile without changing the levels of C-reactive protein and fibrinogen.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/diagnóstico , Hipoglicemiantes/efeitos adversos , Síndrome Metabólica/metabolismo , Metformina/efeitos adversos , Linhagem , Adulto , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/diagnóstico , Diabetes Mellitus Tipo 2/genética , Método Duplo-Cego , Feminino , Fibrinogênio/metabolismo , Humanos , Hipoglicemiantes/farmacologia , Masculino , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/genética , Metformina/farmacologia , Pessoa de Meia-Idade , Fatores de Risco , Estatísticas não ParamétricasRESUMO
Associated with elevated risk of cardiovascular events and cancer, obesity is a worldwide problem affecting developed and developing countries. Microcirculatory vessels, represented by arterioles, capillaries and venules (mean internal diameter < 100 microm), are the place where blood/tissue nutrition and exchange effectively take place. Microvascular dysfunction is an early event in obesity probably secondary to endothelial dysfunction and capillaries rarefaction. New research techniques allow the investigation of the microcirculation in different vascular beds in humans. Studies suggest a link between endothelial dysfunction and visceral obesity. Oxidative stress, inflammation and renin-angiotensin system are among factors considered to be involved on microvascular dysfunction in obesity. Microcirculatory impairment present in obesity suggests that it could be an important causal factor in obesity-related disorders such as insulin resistance and hypertension.
Assuntos
Resistência à Insulina/fisiologia , Microcirculação/fisiologia , Obesidade/fisiopatologia , Tecido Adiposo , Animais , Doenças Cardiovasculares/etiologia , Endotélio Vascular/fisiopatologia , Humanos , Hipertensão/etiologia , Obesidade/complicações , Obesidade/metabolismo , Estresse Oxidativo/fisiologia , Ratos , Fluxo Sanguíneo Regional/fisiologia , Resistência Vascular/fisiologiaRESUMO
Associated with elevated risk of cardiovascular events and cancer, obesity is a worldwide problem affecting developed and developing countries. Microcirculatory vessels, represented by arterioles, capillaries and venules (mean internal diameter < 100 µm), are the place where blood/tissue nutrition and exchange effectively take place. Microvascular dysfunction is an early event in obesity probably secondary to endothelial dysfunction and capillaries rarefaction. New research techniques allow the investigation of the microcirculation in different vascular beds in humans. Studies suggest a link between endothelial dysfunction and visceral obesity. Oxidative stress, inflammation and rennin-angiotensin system are among factors considered to be involved on microvascular dysfunction in obesity. Microcirculatory impairment present in obesity suggests that it could be an important causal factor in obesity-related disorders such as insulin resistance and hypertension.
Associada ao aumento do risco de eventos cardiovasculares e ao câncer, a obesidade é um problema mundial, que atinge tanto países desenvolvidos quanto em desenvolvimento. A microcirculação é composta por arteríolas, capilares e vênulas (diâmetro interno médio < 100 µm) e é o local onde ocorrem a oferta de nutrientes e as trocas entre o tecido e o sangue. A disfunção microcirculatória é um evento precoce na obesidade e este pode ser secundário à disfunção endotelial ou à redução no número de capilares (rarefação capilar). Novas técnicas em pesquisa permitem a avaliação da microcirculação em diferentes leitos vasculares em humanos. Estudos sugerem uma correlação entre disfunção endotelial e obesidade visceral. Acredita-se que o estresse oxidativo, a inflamação e a atividade aumentada do sistema renina-angiotensina estão entre os fatores envolvidos nessa associação. O comprometimento microcirculatório presente na obesidade sugere que esse pode ser um fator causal importante nas desordens relacionadas com a obesidade, como resistência insulínica e hipertensão.
Assuntos
Animais , Humanos , Ratos , Resistência à Insulina/fisiologia , Microcirculação/fisiologia , Obesidade/fisiopatologia , Tecido Adiposo , Doenças Cardiovasculares/etiologia , Endotélio Vascular/fisiopatologia , Hipertensão/etiologia , Obesidade/complicações , Obesidade/metabolismo , Estresse Oxidativo/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Resistência Vascular/fisiologiaRESUMO
OBJECTIVE: To study if metformin, when administered to first-degree relatives of type 2 diabetes mellitus subjects who have metabolic syndrome and normal glucose tolerance, could improve the cardiovascular risk profile and reduce the levels of both C-reactive protein and fibrinogen. INTRODUCTION: Metabolic syndrome is associated with higher cardiovascular morbidity and mortality. Metformin has vasculo-protective effects even in normoglycemic subjects, and C-reactive protein and fibrinogen are considered markers of endothelial injury and inflammation. METHODS: Thirty-one non-diabetic first-degree relatives of type 2 diabetes mellitus subjects with metabolic syndrome were randomized (1:1) and double-blinded for placement in the placebo and metformin groups (850mg bid/±90days); 16 subjects were administered metformin (mean age 40.0 [33.5-50] years; 13 females) and 15 subjects were in the placebo group (mean age 37.0 [32-42] years; 9 females). Blood samples were collected at baseline and at the end of treatment for biochemical analyses, including an assessment of C-reactive protein and fibrinogen levels. RESULTS: Metformin improved the lipid profile and decreased fasting plasma glucose, systolic blood pressure, weight and body mass index without changing body composition. For those in the placebo we identified no changes in fibrinogen (282.2 [220.4-323.7] mg/L vs. 286.7 [249.6-295.1] mg/L; NS) or in C-reactive protein levels (0.68 [0.3-1.2] vs. 0.64 [0.3-1.0] mg/L; NS). The same was also observed for the levels of fibrinogen (303.9 [217.6-347.6] mg/L vs. 290.9 [251.5-301.9] mg/L; NS) and C-reactive proteins (0.78 [0.3-1.1] vs. 0.80 [0.4-0.9] mg/L; NS) in the metformin group. CONCLUSIONS: Metformin treatment in first-degree relatives of type 2 diabetes mellitus sufferers who have metabolic syndrome and normal glucose tolerance improved the cardiovascular risk profile without changing the levels of C-reactive protein and fibrinogen.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Cardiovasculares/prevenção & controle , /diagnóstico , Hipoglicemiantes/efeitos adversos , Síndrome Metabólica/metabolismo , Metformina/efeitos adversos , Linhagem , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/diagnóstico , Método Duplo-Cego , /genética , Fibrinogênio/metabolismo , Hipoglicemiantes/farmacologia , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/genética , Metformina/farmacologia , Fatores de Risco , Estatísticas não ParamétricasRESUMO
Obesity is traditionally linked to diabetes and cardiovascular diseases. Very recent experimental, clinical and epidemiological, sometimes provocative, data challenge this automaticity by showing that not the amount but the distribution of fat is the important determinant. Moderate abdominal fat accumulation may thus be more harmful than even consequent overweight. In view of the worldwide burden of obesity, factors leading to it in children and young adults must urgently be identified. Since obesity is a very complex cardiometabolic situation, this will require to focus investigations on uncomplicated obese subjects and adequate animal models. The recent discovery of intergenerational transmissions of obesity risk factors and also the key role played by gestational and perinatal events (epigenetic factors) give rise to completely new concepts and research avenues. Considering the potential close relationship between microcirculation and tissue metabolism, demonstrations of structural and/or functional abnormalities in microvascular physiology very early in life of subjects at risk for obesity might provide a solid basis for further investigations of such links. Microcirculation(arterioles, capillaries and venules) is conceivably a key compartment determining over one or several decades the translation of genetic and epigenetic factors into fat accumulation. Available animal models should serve to answer this cardinal question.
Assuntos
Gordura Intra-Abdominal/fisiopatologia , Microcirculação/fisiopatologia , Obesidade/fisiopatologia , Animais , Doenças Cardiovasculares/etiologia , Diabetes Mellitus/etiologia , Endotélio Vascular/fisiopatologia , Humanos , Gordura Intra-Abdominal/metabolismo , Microcirculação/metabolismo , Obesidade/genética , Obesidade/metabolismo , Fatores de Risco , Vasoconstrição , VasodilataçãoRESUMO
Obesity is traditionally linked to diabetes and cardiovascular diseases. Very recent experimental, clinical and epidemiological, sometimes provocative, data challenge this automaticity by showing that not the amount but the distribution of fat is the important determinant. Moderate abdominal fat accumulation may thus be more harmful than even consequent overweight. In view of the worldwide burden of obesity, factors leading to it in children and young adults must urgently be identified. Since obesity is a very complex cardiometabolic situation, this will require to focus investigations on uncomplicated obese subjects and adequate animal models. The recent discovery of intergenerational transmissions of obesity risk factors and also the key role played by gestational and perinatal events (epigenetic factors) give rise to completely new concepts and research avenues. Considering the potential close relationship between microcirculation and tissue metabolism, demonstrations of structural and/or functional abnormalities in microvascular physiology very early in life of subjects at risk for obesity might provide a solid basis for further investigations of such links. Microcirculation(arterioles, capillaries and venules) is conceivably a key compartment determining over one or several decades the translation of genetic and epigenetic factors into fat accumulation. Available animal models should serve to answer this cardinal question.
A obesidade é tradicionalmente associada ao diabetes e adoenças cardiovasculares. Dados muito recentes, algumasvezes provocativos, experimentais, clínicos e epidemiológicos questionam essa associação automática mostrando que não é a quantidade, mas a distribuição de gordura que é o determinante importante. O acúmulo moderado de gordura abdominal pode ser mais danoso que o conseqüente sobrepeso. Tendo em vista o aumento mundial da obesidade, fatores que levam a isso em crianças e adultos jovens devem ser urgentemente identificados. Como a obesidade é uma situação cardiometabólica muito complexa, essa identificação deve ser feita em obesos não-complicados e em modelos animais adequados. A recente descoberta da transmissão inter-geração de fatores de risco da obesidade e também do papel fundamental da gestação e de eventos perinatais (fatores epi-genéticos) dão origem a conceitos e linhas de pesquisa completamente novos. Considerando a estreita relação potencial entre a microcirculação e o metabolismo tecidual, demonstrações de anormalidades estruturais e/ou funcionais na fisiologia microvascular muito cedo na vida de pessoas com risco para obesidade podem fornecer uma base sólida para investigações futuras dessas ligações. A microcirculação (arteríolas, capilares e vênulas) é conceitualmente um compartimento chave na determinação em uma ou várias décadas dos fatores genéticos e epi-genéticos em acúmulo de gordura. Os modelos experimentais disponíveis devem servir para responder essa questão extremamente relevante.
Assuntos
Animais , Humanos , Gordura Intra-Abdominal/fisiopatologia , Microcirculação/fisiopatologia , Obesidade/fisiopatologia , Doenças Cardiovasculares/etiologia , Diabetes Mellitus/etiologia , Endotélio Vascular/fisiopatologia , Gordura Intra-Abdominal/metabolismo , Microcirculação/metabolismo , Obesidade/genética , Obesidade/metabolismo , Fatores de Risco , Vasoconstrição , VasodilataçãoRESUMO
PURPOSE: To test the possibility of obtaining a practical and stable model of hyperinsulinemia and hyperglycemia in hamsters, substituting the drinking water by 10% or 20% fructose solutions for a period of 2, 4, or 6 months. METHODS: Male hamsters were divided into 3 main groups, further divided in 3 subgroups: Two months: Group Ia control (n = 51) received filtered water, Group Ib (n = 49) received 10% fructose solution instead of water, Group Ic (n=8) received 20% fructose solution instead of water. Four months: Group IIa control (n=8), Group IIb 10% fructose (n = 7), Group IIc 20% fructose (FIIc, n = 7). Six months: Group IIIa control (n = 6), Group IIIb 10% Fructose (n = 6), Group IIIc 20% Fructose (n = 5). All groups were fed with the same laboratory diet. The animals were weighed every 2 weeks during the study period. On the final day of each experiment (61st, 121st, and 181st day after the beginning of the study, respectively), the animals were weighed and anesthetized for blood collection to determine plasma glucose and insulin after at least a 12-h fast. Ten animals of group Ia and 10 of group Ib were evaluated to determine changes in macromolecular permeability induced by ischemia/reperfusion as measured in the cheek pouch microcirculation. RESULTS: Compared to controls, the animals that drank the 10% or 20% fructose solution had significantly greater weight gain (P < .001), fasting plasma glucose (P < .001) Reperfusion, after 30 min ischemia, resulted in an immediate but reversible increase in postcapillary leakage (L) of 89.0 +/- 2.0 L/cm(2) (group Ia - controls), and 116.5 +/- 4.8 L/cm(2) (group Ib 10% fructose), P < .001. These results suggest that chronic administration of either 10% or 20% fructose solutions could be used to experimentally induce a stable hamster model of hyperinsulinemia and hyperglycemia. CONCLUSION: The model might facilitate the study of basic mechanisms of hyperglycemia and hyperinsulinemia affecting the microvasculature as demonstrated by the findings regarding ischemia/reperfusion after only 2 months of treatment.
Assuntos
Frutose/administração & dosagem , Hiperglicemia/induzido quimicamente , Hiperinsulinismo/induzido quimicamente , Animais , Peso Corporal , Cricetinae , Modelos Animais de Doenças , Masculino , Mesocricetus , Fatores de TempoRESUMO
PURPOSE: To test the possibility of obtaining a practical and stable model of hyperinsulinemia and hyperglycemia in hamsters, substituting the drinking water by 10 percent or 20 percent fructose solutions for a period of 2, 4, or 6 months. METHODS: Male hamsters were divided into 3 main groups, further divided in 3 subgroups: Two months: Group Ia control (n = 51) received filtered water, Group Ib (n = 49) received 10 percent fructose solution instead of water, Group Ic (n=8) received 20 percent fructose solution instead of water. Four months: Group IIa control (n=8), Group IIb 10 percent fructose (n = 7), Group IIc 20 percent fructose (FIIc, n = 7). Six months: Group IIIa control (n = 6), Group IIIb 10 percent Fructose (n = 6), Group IIIc 20 percent Fructose (n = 5). All groups were fed with the same laboratory diet. The animals were weighed every 2 weeks during the study period. On the final day of each experiment (61st, 121st, and 181st day after the beginning of the study, respectively), the animals were weighed and anesthetized for blood collection to determine plasma glucose and insulin after at least a 12-h fast. Ten animals of group Ia and 10 of group Ib were evaluated to determine changes in macromolecular permeability induced by ischemia/reperfusion as measured in the cheek pouch microcirculation. RESULTS: Compared to controls, the animals that drank the 10 percent or 20 percent fructose solution had significantly greater weight gain (P < .001), fasting plasma glucose (P < .001) Reperfusion, after 30 min ischemia, resulted in an immediate but reversible increase in postcapillary leakage (L) of 89.0 ± 2.0 L/cm² (group Ia - controls), and 116.5 ± 4.8 L/cm² (group Ib 10 percent fructose), P < .001.These results suggest that chronic administration of either 10 percent or 20 percent fructose solutions could be used to experimentally induce a stable hamster model of hyperinsulinemia and hyperglycemia. CONCLUSION: The model might facilitate...
OBJETIVO: Testar a possibilidade de obtenção de um modelo prático e estável de hiperinsulinemia e hiperglicemia em hamsters substituindo a água de beber por soluções de frutose a 10 por cento ou 20 por cento por um período de dois, quatro ou seis meses. MÉTODOS: Hamsters machos foram divididos em 3 grupos e cada grupo subdividido em 3 subgrupos. Dois meses: Grupo Ia-controle (n=51), recebeu água filtrada, Grupo Ib-(n=49), recebeu solução de frutose a 10 por cento ao invés de água e Grupo Ic-( n=8), recebeu solução de frutose a 20 por cento ao invés de água. Quatro meses: Grupo IIa - controle (n=8), Grupo IIb - 10 por cento frutose (n=7) e Grupo IIc - 20 por cento frutose (n=7). Seis meses: Grupo IIIa - controle (n=6), Grupo IIIb - 10 por cento frutose (n=6) e Grupo IIIc - 20 por cento frutose (n=5). Todos os animais foram alimentados com a mesma dieta padrão de laboratório. Os animais foram pesados a cada 2 semanas durante o período do estudo. No dia do final do experimento (61°, 121° e 181° dia, respectivamente, após o início do estudo), os animais foram pesados e anestesiados para coleta de sangue para determinação da glicose e da insulina sérica, após jejum de pelo menos 12 h. Em 10 animais do grupo Ia e em 10 do grupo Ib avaliamos, na microcirculação da bolsa da bochecha, a variação da permeabilidade a macromoléculas induzida por isquemia/reperfusão. RESULTADOS: Comparados ao grupo controle, os animais que beberam soluções de frutose a 10 ou 20 por cento tiveram um aumento significativo de massa corporal (p<0,001) e da glicemia de jejum (p<0,001). Durante o experimento de reperfusão, após 30 min de isquemia, houve um aumento imediato e reversível do extravasamento (E) pós-capilar de 89,0 ± 2,0 E/cm² (grupo Ia) e 116,5 ± 4,8 E/cm² (grupo Ib), p<0,001. CONCLUSÃO: Esse estudo sugere que a utilização crônica de solução de frutose a 10 por cento ou 20 por cento pode ser usada para induzir experimentalmente um modelo estável de hiperinsulinemia...
Assuntos
Animais , Cricetinae , Masculino , Frutose/administração & dosagem , Hiperglicemia/induzido quimicamente , Hiperinsulinismo/induzido quimicamente , Peso Corporal , Modelos Animais de Doenças , Mesocricetus , Fatores de TempoRESUMO
Obstructive sleep apnea is an increasingly recognized medical problem. The recent attention to its frequency in the general population and its important role in metabolic, vascular, and behavioral aspects have sharply increased the number and nature of investigations, thereby revealing new aspects that open new approaches in research. Whereas obstructive sleep apnea is a well-known phenomenon accompanying obesity and diabetes, new findings strongly suggest that this close relationship may also operate in the opposite direction. Indeed obstructive sleep apnea may be a primary feature inducing or aggravating a series of vascular and metabolic disturbances closely resembling the metabolic syndrome. This review will discuss established and potential mechanisms responsible for these changes. Obstructive sleep apnea indeed appears to gather all the elements necessary to induce insulin resistance, hypertension, and possibly heart failure. After careful analysis of these modifications and considering how they are intertwined, we propose that microcirculation could represent the common denominator mediating the progression of this pathology, as it is eventually the case in the metabolic syndrome and diabetes domain. This plausible hypothesis is discussed in detail and should be verified by appropriate preclinical and clinical protocols, which are now achievable by using noninvasive techniques in humans.
Assuntos
Doenças Cardiovasculares/etiologia , Síndrome Metabólica/etiologia , Microcirculação/fisiopatologia , Apneia Obstrutiva do Sono/complicações , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Humanos , Resistência à Insulina , Síndrome Metabólica/metabolismo , Síndrome Metabólica/fisiopatologia , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/fisiopatologiaRESUMO
A apnéia obstrutiva do sono é um problema médico cujo reconhecimento tem aumentado. As últimas pesquisas mostrando sua freqüência na população em geral e seu importante papel metabólico, vascular e comportamental aumentou o número e a natureza das investigações revelando, assim, novos aspectos que abrem caminhos para estudos. Embora a apnéia obstrutiva do sono seja um fenômeno bem conhecido acompanhando diabetes e obesidade, novas descobertas sugerem que esta relação causal pode também ser verdadeira no sentido inverso. Na realidade, a apnéia obstrutiva do sono pode ser o marco inicial ou primário que induz ou agrava uma série de distúrbios vasculares e metabólicos que se aproximam da síndrome metabólica. Esta revisão discutirá mecanismos estabelecidos e potenciais responsáveis por estas mudanças. A apnéia obstrutiva do sono parece realmente juntar todos os elementos necessários para induzir resistência à insulina, hipertensão e possivelmente insuficiência cardíaca. Após análise cuidadosa destas modificações, considerando que as mesmas são interligadas, propomos que a microcirculação, como ocorre nos casos de síndrome metabólica e diabetes, poderia representar o denominador comum que mediaria a progressão desta patologia. Esta hipótese é discutida em detalhe e deve ser verificada em estudos pré-clínicos e clínicos apropriados que são atualmente possíveis usando técnicas não-invasivas em humanos.
Assuntos
Humanos , Doenças Cardiovasculares/etiologia , Síndrome Metabólica/etiologia , Microcirculação/fisiopatologia , Apneia Obstrutiva do Sono/complicações , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Resistência à Insulina , Síndrome Metabólica/metabolismo , Síndrome Metabólica/fisiopatologia , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/fisiopatologiaRESUMO
OBJECTIVE: Endothelial dysfunction is an early marker of atherosclerosis seen in type 2 diabetic subjects. Metformin is commonly used in the treatment of type 2 diabetes and has known vasculoprotective effects beyond its hypoglycemic ones. We aimed to investigate the vascular effects of metformin in first-degree relatives with metabolic syndrome of type 2 diabetic patients. RESEARCH DESIGN AND METHODS: The study included 31 subjects (age 38.3 +/- 7.6 years and BMI 36.3 +/- 5.2 kg/m2), who were first-degree relatives of type 2 diabetic patients and who had metabolic syndrome and normal glucose tolerance. The subjects were randomly assigned 1:1 in a double-blind fashion to receive placebo (n = 15) or metformin (n = 16). Endothelial function was assessed by venous occlusion plethysmography, measuring forearm blood flow (FBF) and vascular resistance responses to three intra-arterial infusions of endothelium-dependent (acetylcholine 7.5, 15, and 30 microg/min) and independent (sodium nitroprusside 2, 4, and 8 microg/min) vasodilators. Weight, BMI, systolic and diastolic blood pressure, waist, and laboratory parameters (lipid profile and fasting plasma glucose [FPG]) were assessed at baseline and after treatment. RESULTS: The metformin and placebo groups did not differ in anthropometric, clinical, laboratory, and vascular measurements at baseline. The metformin group had decreased weight, BMI, systolic blood pressure, and FPG and improved lipid profile. Endothelium-dependent FBF responses were also improved, without any effect on endothelium-independent responses. There was no correlation between the improvement on FBF responses and the observed changes on anthropometric, clinical, and laboratory parameters. CONCLUSIONS: We concluded that metformin improved vascular endothelial reactivity in first-degree relatives with metabolic syndrome of type 2 diabetic patients, independently of its known antihyperglycemic effects.