RESUMEN
Excess nutrient uptake is one of the main factors of complications related to metabolism disorders. Therefore, efforts have emerged to modulate nutrient transport in the intestine. However, current approaches are mainly invasive interventions with various side effects. Here, a pH-responsive hydrogel is formulated by acidifying the hydroxide compounds within sucralfate to allow electrostatic interactions between pectin and aluminum ions. The pH responsiveness relies on the alternation of cations and hydroxide species, providing reversible shifting from a hydrogel to a complex coacervate system. It acts as a transient physical barrier coating to inhibit intestinal absorption and changes the viscosity and barrier function in different parts of the gastrointestinal tract, showing enhanced mucoadhesive properties. The therapeutic hydrogel remarkably lowers the immediate blood glucose response by modulating nutrient contact with bowel mucosa, suggesting potential in treating diabetes. In addition, it significantly reduces weight gain, fat accumulation, and hepatic lipid deposition in rodent models. This study provides a novel strategy for fabricating pH-responsive hydrogels, which may serve as a competent candidate for metabolism disorder management.
Asunto(s)
Trastornos del Metabolismo de la Glucosa/prevención & control , Hidrogeles/farmacología , Hidróxidos/farmacología , Pectinas/farmacología , Sucralfato/farmacología , Adhesivos , Animales , Sistemas de Liberación de Medicamentos , Prueba de Tolerancia a la Glucosa , Hidrogeles/síntesis química , Hidrogeles/química , Concentración de Iones de Hidrógeno , Hidróxidos/química , Ensayo de Materiales , Ratones , Estructura Molecular , Imagen Óptica , Pectinas/síntesis química , Pectinas/química , Sucralfato/síntesis química , Sucralfato/químicaRESUMEN
INTRODUCTION: Objectives: low vitamin D during pregnancy is common and could adversely affect health outcomes. This study evaluated vitamin D status during pregnancy and early in life, and its association with glucose metabolism. Methods: maternal serum 25(OH)D, glucose, and insulin levels were measured longitudinally during pregnancy in Hispanic women with overweight/obesity (n = 31) and their infants at birth and 4 months. Results: insulin and HOMA-IR levels were higher among women with vitamin D below adequate levels compared to those with adequate levels in pregnancy (p < 0.05). Late in pregnancy, as vitamin D increased by one unit (ng/mL), insulin decreased by 0.44 units and HOMA-IR by 0.09 units. Maternal vitamin D late in pregnancy was correlated with infant vitamin D levels at birth (r = 0.89; p < 0.01) and 4 months (r = 0.9; p = 0.04), and with glucose (r = 0.79; p = 0.03) and insulin (r = 0.83; p = 0.04) at 4 months. Conclusion: maternal vitamin D status was associated with maternal and infant glucose metabolism in this sample.
INTRODUCCIÓN: Objetivos: un bajo nivel de vitamina D durante el embarazo es común y puede tener consecuencias adversas en la salud. Este estudio evaluó el nivel de vitamina D en mujeres embarazadas y sus bebés, así como su asociación con los marcadores de glucosa. Métodos: los niveles séricos de 25(OH)D, glucosa e insulina se midieron longitudinalmente en mujeres embarazadas hispanoamericanas con sobrepeso/obesidad (n = 31) y en sus bebés, desde el nacimiento hasta los 4 meses de edad, en Puerto Rico. Resultados: los niveles maternos de insulina y HOMA-IR eran mayores en las mujeres con niveles de vitamina D por debajo de lo considerado adecuado, comparado con aquellas con niveles adecuados durante todo el embarazo (p < 0,05). Al final del embarazo, a medida que los niveles de vitamina D aumentaron, por cada unidad (ng/mL) de aumento, la insulina disminuyo en 0,44 unidades y el HOMA-IR en 0,09 unidades. El nivel de vitamina D al final del embarazo se correlacionó con los niveles del bebé al nacer (r = 0,89; p < 0,01) y a los 4 meses (r = 0,9; p = 0,04), y con los niveles de glucosa (r = 0,79; p = 0,03) e insulina (r = 0,83; p = 0,04) a los 4 meses. Conclusión: el nivel materno de vitamina D se asoció con los marcadores maternos e infantiles de glucosa en esta muestra.
Asunto(s)
Trastornos del Metabolismo de la Glucosa/prevención & control , Mujeres Embarazadas , Vitamina D/análisis , Adulto , Biomarcadores/análisis , Biomarcadores/sangre , Glucemia/análisis , Correlación de Datos , Femenino , Trastornos del Metabolismo de la Glucosa/sangre , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Masculino , Puerto Rico/etnología , Vitamina D/sangre , Deficiencia de Vitamina D/sangreRESUMEN
Timely diagnosis of type 2 diabetes and early intervention and treatment of it are important for controlling metabolic disorders, delaying and reducing complications, reducing mortality, and improving quality of life. Type 2 diabetes was diagnosed by Fourier transform mid-infrared (FTIR) attenuated total reflection (ATR) spectroscopy in combination with extreme gradient boosting (XGBoost). Whole blood FTIR-ATR spectra of 51 clinically diagnosed type 2 diabetes and 55 healthy volunteers were collected. For the complex composition of whole blood and much spectral noise, Savitzky-Golay smoothing was first applied to the FTIR-ATR spectrum. Then PCA was used to eliminate redundant data and got the best number of principle components. Finally, the XGBoost algorithm was used to discriminate the type 2 diabetes from healthy volunteers and the grid search algorithm was used to optimize the relevant parameters of the XGBoost model to improve the robustness and generalization ability of the model. The sensitivity of the optimal XGBoost model was 95.23% (20/21), the specificity was 96.00% (24/25), and the accuracy was 95.65% (44/46). The experimental results show that FTIR-ATR spectroscopy combined with XGBoost algorithm can diagnose type 2 diabetes quickly and accurately without reagents.
Asunto(s)
Análisis Químico de la Sangre/instrumentación , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Adulto , Algoritmos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/psicología , Femenino , Trastornos del Metabolismo de la Glucosa/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Sensibilidad y EspecificidadRESUMEN
BACKGROUND AND PURPOSE: Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis, is closely related to metabolic diseases such as obesity and diabetes. Despite an accumulating number of studies, no pharmacotherapy that targets NAFLD has received general approval for clinical use. EXPERIMENTAL APPROACH: Inhibition of the sodium-glucose cotransporter 2 (SGLT2) is a promising approach to treat diabetes, obesity, and associated metabolic disorders. In this study, we investigated the effect of a novel SGLT2 inhibitor, NGI001, on NAFLD and obesity-associated metabolic symptoms in high-fat diet (HFD)-induced obese mice. KEY RESULTS: Delayed intervention with NGI001 protected against body weight gain, hyperglycaemia, hyperlipidaemia, and hyperinsulinaemia, compared with HFD alone. Adipocyte hypertrophy was prevented by administering NGI001. NGI001 inhibited impaired glucose metabolism and regulated the secretion of adipokines associated with insulin resistance. In addition, NGI001 supplementation suppressed hepatic lipid accumulation and inflammation but had little effect on kidney function. In-depth investigations showed that NGI001 ameliorated fat deposition and increased AMPK phosphorylation, resulting in phosphorylation of its major downstream target, acetyl-CoA carboxylase, in human hepatocyte HuS-E/2 cells. This cascade ultimately led to the down-regulation of downstream fatty acid synthesis-related molecules and the up-regulation of downstream ß oxidation-associated molecules. Surprisingly, NGI001 decreased gene and protein expression of SGLT1 and SGLT2 and glucose uptake in oleic acid-treated HuS-E/2 cells. CONCLUSION AND IMPLICATIONS: Our findings suggest the novel SGLT2 inhibitor, NGI001 has therapeutic potential to attenuate or delay the onset of diet-induced metabolic diseases and NAFLD.
Asunto(s)
Tejido Adiposo/efectos de los fármacos , Dieta Alta en Grasa , Metabolismo Energético/efectos de los fármacos , Hígado/efectos de los fármacos , Síndrome Metabólico/prevención & control , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Transportador 2 de Sodio-Glucosa/metabolismo , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Animales , Biomarcadores/sangre , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Línea Celular , Modelos Animales de Enfermedad , Dislipidemias/etiología , Dislipidemias/metabolismo , Dislipidemias/prevención & control , Trastornos del Metabolismo de la Glucosa/etiología , Trastornos del Metabolismo de la Glucosa/metabolismo , Trastornos del Metabolismo de la Glucosa/prevención & control , Humanos , Resistencia a la Insulina , Lípidos/sangre , Hígado/metabolismo , Hígado/patología , Masculino , Síndrome Metabólico/etiología , Síndrome Metabólico/metabolismo , Síndrome Metabólico/patología , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patologíaRESUMEN
Solid tumour frequently undergoes metabolic stress during tumour development because of inadequate blood supply and the high nutrient expenditure. p53 is activated by glucose limitation and maintains cell survival via triggering metabolic checkpoint. However, the exact downstream contributors are not completely identified. BAG3 is a cochaperone with multiple cellular functions and is implicated in metabolic reprogramming of pancreatic cancer cells. The current study demonstrated that glucose limitation transcriptionally suppressed BAG3 expression in a p53-dependent manner. Importantly, hinderance of its down-regulation compromised cellular adaptation to metabolic stress triggered by glucose insufficiency, supporting that BAG3 might be one of p53 downstream contributors for cellular adaptation to metabolic stress. Our data showed that ectopic BAG3 expression suppressed p53 accumulation via direct interaction under metabolic stress. Thereby, the current study highlights the significance of p53-mediated BAG3 suppression in cellular adaptation to metabolic stress via facilitating p53 accumulation.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Reguladoras de la Apoptosis/genética , Regulación de la Expresión Génica , Trastornos del Metabolismo de la Glucosa/prevención & control , Transcripción Genética , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Adaptadoras Transductoras de Señales/antagonistas & inhibidores , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Apoptosis , Proteínas Reguladoras de la Apoptosis/antagonistas & inhibidores , Proteínas Reguladoras de la Apoptosis/metabolismo , Ciclo Celular , Movimiento Celular , Proliferación Celular , Trastornos del Metabolismo de la Glucosa/etiología , Trastornos del Metabolismo de la Glucosa/metabolismo , Trastornos del Metabolismo de la Glucosa/patología , Células HCT116 , Humanos , Células MCF-7 , Proteína p53 Supresora de Tumor/genéticaRESUMEN
BACKGROUND: Olanzapine, regarded as one of the most efficacious antipsychotic medications for the treatment of schizophrenia, is associated with a high risk of weight gain and metabolic dysfunction. ALKS 3831, a clinical candidate for treatment of schizophrenia, is a combination of olanzapine and samidorphan, an opioid receptor antagonist. The addition of samidorphan is intended to mitigate weight gain and the metabolic dysregulation associated with the use of olanzapine. METHODS: Non-clinical studies were conducted to assess the metabolic effects of olanzapine and samidorphan alone and in combination at clinically relevant exposure levels. RESULTS: Chronic olanzapine administration in male and female rats shifted body composition by increasing adipose mass, which was accompanied by an increase in the rate of weight gain in female rats. Co-administration of samidorphan normalized body composition in both sexes and attenuated weight gain in female rats. In hyperinsulinemic euglycemic clamp experiments conducted prior to measurable changes in weight and/or body composition, olanzapine decreased hepatic insulin sensitivity and glucose uptake in muscle while increasing uptake in adipose tissue. Samidorphan appeared to normalize glucose utilization in both tissues, but did not restore hepatic insulin sensitivity. In subsequent studies, samidorphan normalized olanzapine-induced decreases in whole-body glucose clearance following bolus insulin administration. Results from experiments in female monkeys paralleled the effects in rats. CONCLUSIONS: Olanzapine administration increased weight gain and adiposity, both of which were attenuated by samidorphan. Furthermore, the combination of olanzapine and samidorphan prevented olanzapine-induced insulin insensitivity. Collectively, these data indicate that samidorphan mitigates several metabolic abnormalities associated with olanzapine in both the presence and the absence of weight gain.
Asunto(s)
Tejido Adiposo/efectos de los fármacos , Antipsicóticos/efectos adversos , Trastornos del Metabolismo de la Glucosa , Naltrexona/análogos & derivados , Antagonistas de Narcóticos/farmacología , Olanzapina/efectos adversos , Aumento de Peso/efectos de los fármacos , Animales , Combinación de Medicamentos , Femenino , Trastornos del Metabolismo de la Glucosa/inducido químicamente , Trastornos del Metabolismo de la Glucosa/tratamiento farmacológico , Trastornos del Metabolismo de la Glucosa/prevención & control , Macaca fascicularis , Masculino , Naltrexona/administración & dosificación , Naltrexona/farmacología , Antagonistas de Narcóticos/administración & dosificación , Ratas , Ratas Sprague-Dawley , Factores SexualesRESUMEN
Overweight and obesity in children is becoming an increasingly common problem due to the increased access to processed food, overly high energy density diet, and limitation of physical activity in children. Such trends in today's society lead to health consequences that can be observed in the early stages of carbohydrate metabolism disorders. Reduction of body weight and changes in eating habits can prevent the onset of type 2 diabetes. Recently, the benefits of consuming products containing resistant starch, which has the main advantage of influencing the metabolic pathway of glucose, have been increasingly underlined. To date, no recommendations have been made for the daily intake of resistant starch or its content in individual products available on the food market. However, in the medical literature, there are an increasing number of reported cases of the beneficial effect of consuming resistant starch as a factor that supports glycaemic control in children with carbohydrate disorders. Unfortunately, the above topic requires further research in this direction, especially in the developmental age population, which will allow the formulation of precise conclusions regarding its use in the prevention of overweight, obesity, carbohydrate metabolism disorders, and the development of diabetes.
Asunto(s)
Conducta Alimentaria , Trastornos del Metabolismo de la Glucosa/prevención & control , Obesidad/prevención & control , Sobrepeso/prevención & control , Almidón , Glucemia , Metabolismo de los Hidratos de Carbono , Ingestión de Alimentos , Trastornos del Metabolismo de la Glucosa/etiología , Índice Glucémico , Conductas Relacionadas con la Salud , Humanos , Obesidad/etiología , Sobrepeso/etiología , Obesidad Infantil/etiología , Obesidad Infantil/prevención & controlRESUMEN
BACKGROUND: N-Acetylcysteine (NAC), an antioxidative reagent for clinical diseases, shows potential in the treatment of diabetes and other metabolic diseases. However, it is unknown how NAC modulates the gut microbiota of mice with metabolic syndrome. The aim of the present study was to demonstrate the preventive effect of NAC on intestinal dysbiosis and glucose metabolic disorder. METHODS: Mice (C57BL/6J strain) were fed either a normal chow diet (NCD), NCD plus NAC, a high-fat diet (HFD), or HFD plus NAC for 5 months, after which glucose levels, circulating endotoxins and key metabolism-related proteins were determined. Fecal samples were analyzed by 16S rRNA sequencing. A novel analysis was performed to predict functional changes in gut microbiota. In addition, Spearman's correlation analysis was performed between metabolic biomarkers and bacterial abundance. RESULTS: Treatment with NAC significantly reversed the glucose intolerance, fasting glucose concentrations, and gains in body weight and plasma endotoxin in HFD-fed mice. Further, NAC upregulated occludin and mucin glycoprotein levels in the proximal colon of HFD-treated mice. Noticeably, NAC promoted the growth of beneficial bacteria (i.e. Akkermansia, Bifidobacterium, Lactobacillus and Allobaculum) and decreased populations of diabetes-related genera, including Desulfovibrio and Blautia. In addition, NAC may affect the metabolic pathways of intestinal bacteria, including lipopolysaccharide biosynthesis, oxidative stress, and bacterial motility. Finally, the modified gut microbiota was closely associated with the metabolic changes in NAC-treated HFD-fed mice. CONCLUSIONS: N-Acetylcysteine may be a potential drug to prevent glucose metabolic disturbances by reshaping the structure of the gut microbiota.
Asunto(s)
Acetilcisteína/farmacología , Dieta Alta en Grasa/efectos adversos , Disbiosis/prevención & control , Microbioma Gastrointestinal/efectos de los fármacos , Trastornos del Metabolismo de la Glucosa/prevención & control , Acetilcisteína/administración & dosificación , Animales , Bacterias/clasificación , Bacterias/efectos de los fármacos , Bacterias/genética , Glucemia/análisis , Disbiosis/metabolismo , Disbiosis/microbiología , Heces/microbiología , Depuradores de Radicales Libres/administración & dosificación , Depuradores de Radicales Libres/farmacología , Microbioma Gastrointestinal/genética , Intolerancia a la Glucosa/sangre , Intolerancia a la Glucosa/prevención & control , Trastornos del Metabolismo de la Glucosa/etiología , Trastornos del Metabolismo de la Glucosa/microbiología , Hiperglucemia/sangre , Hiperglucemia/prevención & control , Lipopolisacáridos/sangre , Ratones Endogámicos C57BL , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: The effectiveness of lifestyle intervention for weight loss on cardiometabolic risk factors among overweight and obese individuals in the community setting remains inconclusive. This study aimed to evaluate the effect of a 6-month weight loss lifestyle intervention on cardiometabolic risk factors among overweight and obese women and the sustainability of the changes in those markers at 12-month follow-up, comparing an intervention group with a control group. METHODS: A total of 243 participants from MyBFF@home were included in this study. Fasting blood samples at baseline, 6- and 12-month were assessed for fasting plasma glucose (FPG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides. The effect of the intervention on cardiometabolic risk markers were investigated within and between study groups using t-test and general linear model (GLM) repeated measure ANOVA. RESULTS: Results from repeated measures ANOVA showed intervention effect only in TC where significant reduction was found in the intervention group (- 0.26 mmol/L [95% CI: - 0.47 to - 0.06], p < 0.01) compared to the control group (- 0.06 mmol/L [95% CI: - 0.28 to 0.17]) at 12 months. At 6 months, TC was reduced significantly in both groups but only intervention group retained the reduction in maintenance phase while, the level increased significantly in the control group (0.22 mmol/L [95% CI: 0.06 to 0.38]). This attributed to significant increase in TC/HDL-C ratio in the control group during maintenance phase (0.32 [95% CI: 0.15 to 0.50], p < 0.001). The intervention group also showed trend of reduction in FPG at 6 months and further decreased during maintenance phase (- 0.19 mmol/L [95% CI: - 0.32 to - 0.06], p < 0.01). At 6 months HDL-C was maintained in the intervention group but reduced significantly in the control group (- 0.05 mmol/L [95% CI: - 0.10 to - 0.01], p < 0.05). No significant difference was detected in both markers when compared between groups. CONCLUSIONS: In the context of low socio-economic communities, this study supports that weight loss related lifestyle modifications over a 6-month period could improve selected cardiometabolic risk factors, particularly fasting glucose, TC and HDL-C in overweight and obese women with favourable sustainability over a 12-month period.
Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Trastornos del Metabolismo de la Glucosa/prevención & control , Estilo de Vida Saludable/fisiología , Obesidad/fisiopatología , Sobrepeso/fisiopatología , Pérdida de Peso/fisiología , Adulto , Femenino , Humanos , Malasia , Persona de Mediana Edad , Factores de Riesgo , Factores SocioeconómicosRESUMEN
Associations between obesity, diabetes type II, and steatosis have long been recognized. However, a pharmacotherapy that acts in a multifactorial manner controlling the interactions between these conditions is not available. A variety of natural plants, functional fatty acids, and other natural dietary compounds have been used in various anti-obesity products. We investigated the effects of oral administration of an antioxidant carotenoid pigment Bixin and Bixin: ß-Cyclodextrin in an obese murine model. C57BL/6 male mice (4-5 weeks) received standard diet (2.18â¯kcal per 1â¯g) (CT) and high-fat diet (4.38â¯kcal per 1â¯g) (CT/OB, BIX and BIX/ßCD) (nâ¯=â¯10 per group). After 16 weeks, the BIX and BIX/ßCD were treated by gavage (100⯵L day-1) for six weeks, with water (CT and CT/OB groups) and (50â¯mgâ¯kg-1 day-1), Bixin (BIX group) or Bix: ß-CD (BIX/ßCD). Body weight, Lee's Index, adiposity, CHT, TG, CHT/HDL-c, glucose levels (metabolic markers) and, liver markers (AST and ALT) were determined. All metabolic and liver parameters exhibited down-regulation after oral administration of BIX and BIX/ßCD. Particularly relevant was Lee's Index and adiposity in BIX- and BIX/ßCD-treated groups (339.18â¯g/cm -BIX and 327.58â¯g/cm -BIX/ßCD vs. 360.68â¯g/cm -CT/OB animals), this finds associated with the insulin sensitivity test, showed a clear association between reduction of adipose tissue and decrease of peripherical insulin resistant. In conclusion, our study suggested that the oral administration of the Bixin and Bix: ß-CD inclusion compound improved the metabolic parameters evaluate in obese mice, being more palatable and hepatoprotective.
Asunto(s)
Glucemia/efectos de los fármacos , Carotenoides/farmacología , Dieta Alta en Grasa , Hígado Graso/prevención & control , Trastornos del Metabolismo de la Glucosa/prevención & control , Hipoglucemiantes/farmacología , Hipolipemiantes/farmacología , Lípidos/sangre , Hígado/efectos de los fármacos , Obesidad/tratamiento farmacológico , beta-Ciclodextrinas/farmacología , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Adipocitos/patología , Adiposidad/efectos de los fármacos , Animales , Biomarcadores/sangre , Glucemia/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Hígado Graso/sangre , Hígado Graso/etiología , Hígado Graso/patología , Trastornos del Metabolismo de la Glucosa/sangre , Trastornos del Metabolismo de la Glucosa/etiología , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/sangre , Obesidad/etiología , Obesidad/patología , Factores de TiempoRESUMEN
Although metabolic syndrome (MetS) could be handled by lifestyle interventions, its relationship with dietary patterns remains unclear in populations from Central Europe. Using data from the Kardiovize Brno cohort, the present study aims to identify the main dietary patterns and to evaluate their association with MetS risk in a random urban sample from Brno, Czech Republic. In a cross-sectional study of 1934 subjects aged 25â»65 years (44.3% male), dietary patterns were derived by food frequency questionnaire (FFQ) administration and principal component analysis. Metabolic syndrome was defined according to the International Diabetes Federation statement. Logistic regression models were applied. High adherence to the prudent dietary pattern was associated with lower odds of abdominal obesity, abnormal glucose concentration, and MetS. By contrast, high adherence to the western dietary pattern was associated with higher odds of abnormal glucose, triglycerides and blood pressure levels. Whilst our results confirm the deleterious effect of a western dietary pattern on several metabolic risk factors, they also indicate that the consumption of a diet rich in cereals, fish, fruit and vegetables is associated with a healthier metabolic profile. However, further prospective research is warranted to develop and validate novel potential preventive strategies against MetS and its complications.
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Conducta Alimentaria , Síndrome Metabólico/epidemiología , Adulto , Anciano , Distribución de Chi-Cuadrado , Estudios Transversales , República Checa/epidemiología , Encuestas sobre Dietas , Dieta Saludable , Dislipidemias/epidemiología , Dislipidemias/prevención & control , Femenino , Trastornos del Metabolismo de la Glucosa/epidemiología , Trastornos del Metabolismo de la Glucosa/prevención & control , Humanos , Hipertensión/epidemiología , Hipertensión/prevención & control , Modelos Logísticos , Masculino , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/prevención & control , Persona de Mediana Edad , Valor Nutritivo , Obesidad Abdominal/epidemiología , Obesidad Abdominal/prevención & control , Oportunidad Relativa , Análisis de Componente Principal , Factores Protectores , Factores de Riesgo , Conducta de Reducción del Riesgo , Salud UrbanaRESUMEN
Obesity and its consequent type 2 diabetes are significant threats to global health. Emerging evidence indicates that ginsenosides from ginseng (Panax ginseng) have anti-diabetic activity. We hypothesized that ginsenosides Rg1 could suppress dietary-induced obesity and improve obesity-related glucose metabolic disorders. Our results showed that ginsenoside Rg1 attenuated dietary-induced body weight gain and fat accumulation in white adipocyte tissue of mice fed a high-fat diet. Furthermore, we found that ginsenosides Rg1 not only decreased fasting glucose concentration and the 2-h postprandial glucose concentration, but also improved insulin resistance and glucose intolerance in those mice. Ginsenoside Rg1 also activated the AMPK pathway in vitro and in vivo and increased plasma membrane translocation of GLUT4 in C2C12 skeletal muscle cells. In conclusion, our observations suggested that ginsenoside Rg1 inhibited dietary-induced obesity and improved obesity-related insulin resistance and glucose intolerance by activation of the AMPK pathway.
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Dieta Alta en Grasa , Ginsenósidos/farmacología , Trastornos del Metabolismo de la Glucosa/prevención & control , Obesidad/complicaciones , Proteínas Quinasas Activadas por AMP/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Trastornos del Metabolismo de la Glucosa/etiología , Trastornos del Metabolismo de la Glucosa/metabolismo , Resistencia a la Insulina , Masculino , Ratones , Obesidad/metabolismo , Transducción de Señal , Factores de TiempoRESUMEN
Evidence from observational and intervention studies has shown a high intake of tree nuts is associated with a reduced risk of cardiovascular disease (CVD), mortality from type 2 diabetes (T2DM), and all-cause mortality. However, there is limited data regarding their effects on indicators of cardiometabolic risk other than hypercholesterolemia, and little is known about the demonstrable health benefits of pecans (Carya illinoensis (Wangenh.) K.Koch). We conducted a randomized, controlled feeding trial to compare the effects of a pecan-rich diet with an isocaloric control diet similar in total fat and fiber content, but absent nuts, on biomarkers related to CVD and T2DM risk in healthy middle-aged and older adults who are overweight or obese with central adiposity. After 4 weeks on a pecan-rich diet, changes in serum insulin, insulin resistance (HOMA-IR) and beta cell function (HOMA-ß) were significantly greater than after the control diet (p < 0.05). Pecan consumption also lowered the risk of cardiometabolic disease as indicated by a composite score reflecting changes in clinically relevant markers. Thus, compared to the control diet, the pecan intervention had a concurrent and clinically significant effect on several relevant markers of cardiometabolic risk.
Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Carya , Alimentos Funcionales , Trastornos del Metabolismo de la Glucosa/prevención & control , Resistencia a la Insulina , Nueces , Obesidad Abdominal/dietoterapia , Adiposidad , Anciano , Biomarcadores/sangre , Índice de Masa Corporal , Boston/epidemiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Estudios de Cohortes , Estudios Cruzados , Fenómenos Fisiológicos Nutricionales del Anciano , Femenino , Trastornos del Metabolismo de la Glucosa/epidemiología , Trastornos del Metabolismo de la Glucosa/etiología , Humanos , Masculino , Persona de Mediana Edad , Obesidad Abdominal/sangre , Obesidad Abdominal/metabolismo , Obesidad Abdominal/fisiopatología , Sobrepeso/sangre , Sobrepeso/dietoterapia , Sobrepeso/metabolismo , Sobrepeso/fisiopatología , Factores de Riesgo , Método Simple CiegoRESUMEN
Recent years, studies have demonstrated that hyperglycemia is one of the main manifestations after cardiac surgeries, which contributes to myocardial injuries and increases the chance of subsequent complications and mortality in such patients. However, strategies targeting at glucose metabolic disorder after cardiac surgeries to attenuate myocardial injuries are inadequately studied. In this study, a rat model of cardiopulmonary bypass (CPB) was applied to investigate the role of Adenosine 5'-monophosphate-activated protein kinase (AMPK) in modulating myocardial glucose metabolic-induced cardiac injuries after cardiac surgery. The results revealed that CPB elicited significant cardiac dysfunction, and pronouncedly elevated the markers of myocardial injuries including serum creatine kinase MB and cardiac troponin I. Additionally, blunted myocardial glucose uptake after CPB was associated with decreased membrane glucose transporter 4 (GLUT4) content. However, pretreatment of AMPK agonist 5-aminoimidazole-4-carboxamide1-ß-D-ribofuranoside (AICAR) at the beginning of CPB activated AMPK, enhanced phosphorylation of Akt substrate 160 (AS160), and increased myocardial membrane content of GLUT4. Meanwhile, improved myocardial glucose uptake and more importantly alleviated cardiac injury were also observed after CPB pretreated with AICAR. Moreover, the application of a mutant form of AS160 (AS160-4P) abolished the beneficial effect of AICAR, as evidenced by impaired cardiac glucose uptake, reduced myocardial membrane GLUT-4 translocation, increased cardiac injury markers, and deterioration of cardiac function after CPB. In conclusion, it was suggested in this study that preactivation of AMPK by AICAR improved myocardial glucose uptake by promoting AS160 dependent myocardial membrane GLUT-4 translocation, which ultimately provided a potent cardioprotective effect.
Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Aminoimidazol Carboxamida/análogos & derivados , Glucemia/efectos de los fármacos , Puente Cardiopulmonar/efectos adversos , Activadores de Enzimas/farmacología , Trastornos del Metabolismo de la Glucosa/prevención & control , Cardiopatías/prevención & control , Miocardio/enzimología , Ribonucleótidos/farmacología , Adenosina Trifosfato/metabolismo , Aminoimidazol Carboxamida/farmacología , Animales , Glucemia/metabolismo , Forma MB de la Creatina-Quinasa/sangre , Modelos Animales de Enfermedad , Activación Enzimática , Proteínas Activadoras de GTPasa/metabolismo , Trastornos del Metabolismo de la Glucosa/sangre , Trastornos del Metabolismo de la Glucosa/enzimología , Transportador de Glucosa de Tipo 4/metabolismo , Cardiopatías/enzimología , Cardiopatías/patología , Cardiopatías/fisiopatología , Masculino , Miocardio/patología , Fosforilación , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Troponina I/sangreRESUMEN
Obesity and its consequent type 2 diabetes are significant threats to global health. Emerging evidence indicates that ginsenosides from ginseng (Panax ginseng) have anti-diabetic activity. We hypothesized that ginsenosides Rg1 could suppress dietary-induced obesity and improve obesity-related glucose metabolic disorders. Our results showed that ginsenoside Rg1 attenuated dietary-induced body weight gain and fat accumulation in white adipocyte tissue of mice fed a high-fat diet. Furthermore, we found that ginsenosides Rg1 not only decreased fasting glucose concentration and the 2-h postprandial glucose concentration, but also improved insulin resistance and glucose intolerance in those mice. Ginsenoside Rg1 also activated the AMPK pathway in vitro and in vivo and increased plasma membrane translocation of GLUT4 in C2C12 skeletal muscle cells. In conclusion, our observations suggested that ginsenoside Rg1 inhibited dietary-induced obesity and improved obesity-related insulin resistance and glucose intolerance by activation of the AMPK pathway.
Asunto(s)
Animales , Masculino , Ratones , Dieta Alta en Grasa , Ginsenósidos/farmacología , Trastornos del Metabolismo de la Glucosa/prevención & control , Obesidad/complicaciones , Proteínas Quinasas Activadas por AMP/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Trastornos del Metabolismo de la Glucosa/etiología , Trastornos del Metabolismo de la Glucosa/metabolismo , Resistencia a la Insulina , Obesidad/metabolismo , Transducción de Señal , Factores de TiempoRESUMEN
Data on cardiovascular disease in primary hyperparathyroidism (PHPT) are controversial; indeed, at present, cardiovascular involvement is not included among the criteria needed for parathyroidectomy. Aim of this narrative review is to analyze the available literature in an effort to better characterize cardiovascular involvement in PHPT. Due to physiological effects of both parathyroid hormone (PTH) and calcium on cardiomyocyte, cardiac conduction system, smooth vascular, endothelial and pancreatic beta cells, a number of data have been published regarding associations between symptomatic and mild PHPT with hypertension, arrhythmias, endothelial dysfunction (an early marker of atherosclerosis), glucose metabolism impairment and metabolic syndrome. However, the results, mainly derived from observational studies, are inconsistent. Furthermore, parathyroidectomy resulted in conflicting outcomes, which may be linked to several potential biases. In particular, differences in the methods utilized for excluding confounding co-existing cardiovascular risk factors together with differences in patient characteristics, with varying degrees of hypercalcemia, may have contributed to these discrepancies. The only meta-analysis carried out in PHPT patients, revealed a positive effect of parathyroidectomy on left ventricular mass index (a predictor of cardiovascular mortality) and more importantly, that the highest pre-operative PTH levels were associated with the greatest improvements. In normocalcemic PHPT, it has been demonstrated that cardiovascular risk factors are almost similar compared to hypercalcemic PHPT, thus strengthening the role of PTH in the cardiovascular involvement. Long-term longitudinal randomized trials are needed to determine the impact of parathyroidectomy on cardiovascular diseases and mortality in PHPT.
Asunto(s)
Enfermedades Cardiovasculares/etiología , Medicina Basada en la Evidencia , Hiperparatiroidismo Primario/fisiopatología , Animales , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Terapia Combinada/efectos adversos , Trastornos del Metabolismo de la Glucosa/epidemiología , Trastornos del Metabolismo de la Glucosa/etiología , Trastornos del Metabolismo de la Glucosa/prevención & control , Humanos , Hipercalcemia/etiología , Hipercalcemia/prevención & control , Hiperparatiroidismo Primario/sangre , Hiperparatiroidismo Primario/cirugía , Hiperparatiroidismo Primario/terapia , Hormona Paratiroidea/sangre , Paratiroidectomía/efectos adversos , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
Circadian disruption is associated with metabolic disturbances such as hepatic steatosis (HS), obesity and type 2 diabetes. We hypothesized that HS, resulting from constant light (LL) exposure is due to an inconsistency between signals related to food intake and endocrine-driven suprachiasmatic nucleus (SCN) outputs. Indeed, exposing rats to LL induced locomotor, food intake and hormone arrhythmicity together with the development of HS. We investigated whether providing temporal signals such as 12-h food availability or driving a corticosterone plus melatonin rhythm could restore rhythmicity and prevent the metabolic disturbances under LL conditions in male rats. Discrete metabolic improvements under these separate treatments stimulated us to investigate whether the combination of hormone treatment together with mealtime restriction (12-h food during four weeks) could prevent the metabolic alterations. LL exposed arrhythmic rats, received daily administration of corticosterone (2.5 µg/kg) and melatonin (2.5 mg/kg) in synchrony or out of synchrony with their 12-h meal. HS and other metabolic alterations were importantly ameliorated in LL-exposed rats receiving hormonal treatment in synchrony with 12-h restricted mealtime, while treatment out of phase with meal time did not. Interestingly, liver bile acids, a major indication for HS, were only normalized when animals received hormones in synchrony with food indicating that disrupted bile acid metabolism might be an important mechanism for the HS induction under LL conditions. We conclude that food-elicited signals, as well as hormonal signals, are necessary for liver synchronization and that HS arises when there is conflict between food intake and the normal pattern of melatonin and corticosterone.
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Trastornos Cronobiológicos/complicaciones , Corticosterona/administración & dosificación , Hígado Graso/etiología , Métodos de Alimentación , Melatonina/administración & dosificación , Núcleo Supraquiasmático/fisiopatología , Adiposidad/efectos de los fármacos , Animales , Trastornos Cronobiológicos/fisiopatología , Trastornos Cronobiológicos/prevención & control , Hígado Graso/metabolismo , Hígado Graso/prevención & control , Trastornos del Metabolismo de la Glucosa/etiología , Trastornos del Metabolismo de la Glucosa/prevención & control , Luz/efectos adversos , Masculino , Ratas WistarRESUMEN
Introducción: en la actualidad, en Cuba no existe una estrategia establecida para la pesquisa de las alteraciones del metabolismo de la glucosa. Objetivo: evaluar la capacidad diagnóstica de tres metodologías para predecir el riesgo de alteraciones del metabolismo de la glucosa en sujetos con sobrepeso y obesidad. Métodos: se realizó un estudio de evaluación diagnóstica longitudinal, con los datos de 90 sujetos con edades comprendidas entre 25 y 70 años, analizados 2,5 años después de la evaluación inicial. Se obtuvo la edad, el sexo, los antecedentes patológicos personales, los medicamentos empleados, el peso, la talla, el perímetro de cintura y la tensión arterial, así como las concentraciones de glucosa al inicio y a los 2,5 años ulteriores, la insulina y los triglicéridos, además de calcular la resistencia a la insulina en la evaluación inicial. Se utilizó un modelo de puntaje-riesgo para la diabetes tipo 2. Resultados: la frecuencia de alteraciones del metabolismo de la glucosa (glucemia alterada en ayuna y diabetes tipo 2) a los 2,5 años ulteriores, de acuerdo con la presencia previa o no en los sujetos de glucemia alterada en ayunas, resistencia a la insulina y riesgo moderado/alto de diabetes tipo 2, fue superior en los sujetos con glucemia alterada en ayuna previa (72,4 por ciento [21/29]), con resistencia a la insulina al inicio (65,6 por ciento [40/61]) y con riesgo moderado/alto (54,4 por ciento [43/79]), en relación con aquellos sin glucemia alterada en ayuna, sin resistencia a la insulina y con riesgo bajo de diabetes (41,0 por ciento [25/61], p= 0,005; 20,7 por ciento [6/29], p= 0,006 y 27,3 por ciento [3/11], p< 0,0001 respectivamente). La resistencia a la insulina y el riesgo de diabetes tipo 2 moderado/alto mostraron una elevada sensibilidad para identificar sujetos con alteraciones del metabolismo de la glucosa (87,0 y 93,5 por ciento respectivamente), por el contrario de la glucemia alterada en ayunas, que mostró una baja sensibilidad (45,7 por ciento). De los 19 sujetos que desarrollaron diabetes tipo 2 a los 2,5 años, el 100 por ciento presentó riesgo de diabetes tipo 2 moderado/alto y 94,7 por ciento resistencia a la insulina al inicio. Conclusiones: la resistencia a la insulina y el riesgo de diabetes tipo 2 podrían ser de gran utilidad en la identificación de individuos con alto riesgo para padecer diabetes(AU)
Introduction: at present, there is no set strategy in Cuba for the screening of impaired glucose metabolism. Objective: to evaluate the diagnostic capacity of three methodologies to predict the risk of impaired glucose metabolism in overweighed and obese individuals. Methods: a longitudinal diagnostic evaluation study was carried out using data from 90 subjects aged 25 to 70 years, which were analyzed two and a half years after the initial assessment. Information about age, sex, personal pathological history, used medication, weight, height, waist circumference and blood pressure as well the glucose concentrations at the beginning and two and a half years later, insulin and triglyceride indexes was collected in addition to estimating the insulin-resistance index in the initial evaluation. A risk-score model for type 2 diabetes was also used. Results: the frequency of impaired glucose metabolism (impaired fasting glycemia and type 2 diabetes) after two and a half years, according to the previous existence or not of impaired fasting glycemia, insulin resistance and moderate/high risk of type 2 diabetes, was higher in subjects with previous impaired fasting glycemia (72,4 percent [21/29]), with insulin resistance at the beginning (65.6 percent [40/61]) and with moderate/high risk (54,4 percent [43/79]) than in those individuals without impaired fasting glycemia, insulin resistance and with low diabetes risk (41.0 percent [25/61], p= 0,005; 20.7 percent [6/29], p= 0.006 and 27.3 percent [3/11], p< 0.0001, respectively). Insulin resistance index and moderate/high risk of type 2 diabetes showed high sensitivity to identify subjects with impaired glucose metabolism (87.0 and 93.5 percent, respectively), in contrast to impaired fasting glucose whose sensitivity was low (45.7 percent). Of 19 individuals who developed type 2 diabetes two and a half years later, 100 percent had moderate/high risk of type 2 diabetes and 94.7 percent had insulin resistance at the beginning. Conclusions: insulin resistance and risk of type 2 diabetes could be very useful in detecting individuals with high risk of developing diabetes(AU)
Asunto(s)
Humanos , Adulto , Persona de Mediana Edad , Anciano , Factores de Riesgo , Trastornos del Metabolismo de la Glucosa/prevención & control , Diabetes Mellitus Tipo 2/diagnóstico , Sobrepeso/etiología , Obesidad/etiología , Estado Prediabético/prevención & control , Resistencia a la Insulina , Estudios Longitudinales , Estudio de EvaluaciónRESUMEN
This study aimed to review and synthesize the available scientific evidence on the relationship between serum 25(OH)D concentrations and glucose metabolism among adolescents. A total of 19 studies were included. Many studies did not find a relation between 25(OH)D concentrations and insulin sensitivity, but most studies have shown that vitamin D status influences glucose dysregulation in youth due to particularities of this life stage. Considering the prevalence of vitamin D deficiency and insufficiency were high among adolescents, the importance for vitamin D status correction in this young group, in which chronic diseases are not expected but getting every day more common, is mandatory.
Asunto(s)
Fenómenos Fisiológicos Nutricionales de los Adolescentes , Medicina Basada en la Evidencia , Trastornos del Metabolismo de la Glucosa/etiología , Resistencia a la Insulina , Estado Nutricional , Deficiencia de Vitamina D/fisiopatología , Adolescente , Conducta del Adolescente , Desarrollo del Adolescente , Trastornos del Metabolismo de la Glucosa/prevención & control , Humanos , Prevalencia , Conducta Sedentaria , Índice de Severidad de la Enfermedad , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/metabolismoRESUMEN
OBJECTIVES: Interrupting prolonged periods of sitting may improve postprandial insulin and glucose although it is unclear whether interruptions need to involve physical activity or simply a change in posture (from sitting to standing) to benefit adults without metabolic impairment. This study examined effects of interrupting sitting with intermittent walking, and intermittent standing on dynamic insulin and glucose responses in men without known metabolic impairment. DESIGN: A randomised three-arm, cross-over experimental study comprising three seven-hour days of sustained sitting. METHODS: Twenty-five inactive men (aged 40.2±12.2 years) took part. The three interventions were; SIT-ONLY (uninterrupted sitting), SIT-STAND (sitting interrupted with 2min standing bouts every 20min) and SIT-WALK (sitting interrupted with 2min light-intensity walking bouts every 20min). An oral glucose tolerance test was administered at baseline and a standardised mixed test meal at hour three. Comparisons of Matsuda Index, and area under the curve (AUC) for insulin and glucose were made between interventions using generalised estimating equation models. RESULTS: Matsuda index was 16% higher (mean difference 1.2 [95%CI 0.1, 2.2] p=0.02), AUC for glucose 9% lower (-2.5mmol/L×7h [-3.7, -1.3mmol/L×7h] p<0.001) and AUC for insulin 21% lower (-546.5pmol/L×7h [-723.6, -369.3pmol/L×7h] p<0.001) in SIT-WALK compared to SIT-ONLY. There were no significant differences between SIT-STAND and SIT-ONLY in any main outcome measure. CONCLUSIONS: Interrupting sustained sitting with brief repeated bouts of light-intensity walking but not standing reduced insulin demand and improved glucose uptake during a simulated sedentary working day. The benefits of such minor behavioural changes could inform future workplace health interventions.