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Article in Chinese | WPRIM | ID: wpr-878541


In recent years, long non-coding RNA (lncRNA) has been proved to be involved in the regulation of biological processes at various levels, attracting research interests in life science. LncRNA possesses the unique capability and exert discrete effects on transcription, translation and post-translational modification of the target genes through interacting with DNA, RNA and protein. Current studies have revealed that lncRNA plays an important role in hepatic metabolism via diverse pathways. This review focuses on the function of lncRNA and its relationship with hepatic energy metabolism and the correlated diseases, to elucidate the underlying mechanisms and prospects of lncRNA researches.

Glucose/metabolism , Lipid Metabolism/genetics , Liver/metabolism , RNA, Long Noncoding/genetics
Int. j. morphol ; 38(2): 392-399, abr. 2020. tab, graf
Article in English | LILACS | ID: biblio-1056453


The exercise could play a central role to the fat management and glucose metabolism what can be a critical role in the health status of diabetic people, but the high intense exercise remains with controversial data about their effects. To identify the effect of the multimodal high-intensity interval training on body composition, lipid profile, and glucose metabolism in elderly diabetics. Methods: Elderly diabetic individuals (n = 48) were randomly divided in a Sedentary Control (SC) group, a Moderate-Intensity Continuous Training (MICT) group, and a High-Intensity Interval Training (HIIT) group. MICT and HITT were conducted over 60 days, 3x per week, with 40 minutes of exercise. Blood was collected prior to intervention, at four, and at eight weeks subsequently to assess glucose metabolism and lipid profiles. Body composition was determined before and after the intervention period. To verify the normality Kolmogorov-Smirnov statistical test was performed, followed by student "t" test or two-way ANOVA with Bonferroni's post hoc test with significance of 5 % the Cohen's f test to indicate the magnitude of the differences. HIIT significantly lowered cholesterol and triglyceride levels, and significantly lowered blood glucose and glycosylated haemoglobin levels (p<0.05). MICT and HIIT significantly increased levels of high-density lipoprotein, decreased total body mass and body mass index. HIIT resulted in significantly smaller waist circumferences, waist-to-hip ratios, and weight-to-height ratios over 60 days of training. HIIT is more effective than MICT for improving lipid and glycaemic profiles, decreasing body fat, and improving fat distribution elderly diabetics.

El ejercicio podría desempeñar un papel central en el manejo de la grasa y el metabolismo de la glucosa, lo que puede ser un papel crítico en el estado de salud de las personas diabéticas, pero el ejercicio intenso intenso sigue teniendo datos controvertidos sobre sus efectos. El objetivo del estudio fue identificar el efecto del entrenamiento multimodal de intervalos de alta intensidad sobre la composición corporal, el perfil lipídico y el metabolismo de la glucosa en diabéticos de edad avanzada. Los individuos diabéticos de edad avanzada (n = 48) se dividieron aleatoriamente en un grupo de control sedentario (SC), un grupo de entrenamiento continuo de intensidad moderada (MICT) y un grupo de entrenamiento de intervalos de alta intensidad (HIIT). MICT y HITT se realizaron durante 60 días, 3 veces por semana, con 40 minutos de ejercicio. Se recogió sangre antes de la intervención, a las cuatro y a las ocho semanas posteriormente para evaluar el metabolismo de la glucosa y los perfiles de lípidos. La composición corporal se determinó antes y después del período de intervención. Para verificar la normalidad se realizó la prueba estadística de Kolmogorov-Smirnov, seguida de la prueba "t" de Student o ANOVA de dos vías con la prueba post hoc de Bonferroni con una significancia del 5 % de la prueba f de Cohen, indicando las diferencias. HIIT redujo significativamente los niveles de colesterol y triglicéridos, además de reducir de manera importante los niveles de glucosa en la sangre y la hemoglobina glicosilada (p <0.05). MICT y HIIT aumentaron significativamente los niveles de lipoproteína de alta densidad, disminuyeron la masa corporal total y el índice de masa corporal. HIIT resultó en circunferencias de cintura significativamente más pequeñas, relaciones cintura-cadera y relaciones peso-altura durante 60 días de entrenamiento. HIIT es más efectivo que MICT para mejorar los perfiles de lípidos y glucémicos, disminuir la grasa corporal y mejorar la distribución de grasa en los diabéticos de edad avanzada.

Humans , Male , Female , Aged , Body Composition , Diabetes Mellitus , High-Intensity Interval Training/methods , Glycated Hemoglobin A , Exercise , Body Mass Index , Longitudinal Studies , Dyslipidemias/metabolism , Glucose/metabolism
Rev. Assoc. Med. Bras. (1992) ; 66(supl.1): s17-s24, 2020. tab, graf
Article in English | LILACS | ID: biblio-1057108


SUMMARY Type 2 diabetes mellitus is an important public health problem, with a significant impact on cardiovascular morbidity and mortality and an important risk factor for chronic kidney disease. Various hypoglycemic therapies have proved to be beneficial to clinical outcomes, while others have failed to provide an improvement in cardiovascular and renal failure, only reducing blood glucose levels. Recently, sodium-glucose cotransporter-2 (SGLT2) inhibitors, represented by the empagliflozin, dapagliflozin, and canagliflozin, have been showing satisfactory and strong results in several clinical trials, especially regarding the reduction of cardiovascular mortality, reduction of hospitalization due to heart failure, reduction of albuminuria, and long-term maintenance of the glomerular filtration rate. The benefit from SGLT2 inhibitors stems from its main mechanism of action, which occurs in the proximal tubule of the nephron, causing glycosuria, and a consequent increase in natriuresis. This leads to increased sodium intake by the juxtaglomerular apparatus, activating the tubule glomerular-feedback and, finally, reducing intraglomerular hypertension, a frequent physiopathological condition in kidney disease caused by diabetes. In addition, this class of medication presents an appropriate safety profile, and its most frequently reported complication is an increase in the incidence of genital infections. Thus, these hypoglycemic agents gained space in practical recommendations for the management of type 2 diabetes mellitus and should be part of the initial therapeutic approach to provide, in addition to glycemic control, cardiovascular outcomes, and the renoprotection in the long term.

Humans , Cardiovascular Diseases/prevention & control , Diabetes Mellitus, Type 2/drug therapy , Sodium-Glucose Transporter 2/pharmacology , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Hypoglycemic Agents/pharmacology , Kidney Diseases/prevention & control , Benzhydryl Compounds/therapeutic use , Cardiovascular Diseases/etiology , Cardiovascular Diseases/mortality , Diabetes Mellitus, Type 2/complications , Diabetic Nephropathies/etiology , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/prevention & control , Sodium-Glucose Transporter 2/therapeutic use , Canagliflozin/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Glomerular Filtration Rate , Glucose/metabolism , Glucosides/therapeutic use , Hypoglycemic Agents/therapeutic use , Kidney/drug effects , Kidney/physiopathology , Kidney/metabolism , Kidney Diseases/etiology , Kidney Diseases/metabolism
Biol. Res ; 53: 27, 2020. graf
Article in English | LILACS | ID: biblio-1124212


BACKGROUND: Circular RNA (circRNA) is highly expressed in the brain tissue, but its molecular mechanism in cerebral ischemia-reperfusion remains unclear. Here, we explored the role and underlying mechanisms of circRNA antisense non-coding RNA in the INK4 locus (circ_ANRIL) in oxygen-glucose deprivation and reoxygenation (OGD/R)-induced cell injury. RESULTS: The expression of circ_ANRIL in OGD/R-induced human brain microvascular endothelial cells (HBMECs) was significantly up-regulated, while that of miR-622 was significantly down-regulated. Overexpression of circ_ANRIL significantly inhibited the proliferation of OGD/R-induced HBMECs and aggravated OGD/R-induced cell apoptosis. Moreover, circ_ANRIL overexpression further increased the secretion of interleukin (IL)-1ß, IL-6, tumor necrosis factor-a, and monocyte chemoattractant protein-1 in OGD/R-treated HBMECs. The results of bioinformatics analysis and luciferase reporter assay indicated that circ_ANRIL served as an miR-622 sponge to negatively regulate the expression of miR-622 in OGD/R-treated HBMECs. Additionally, circ_ANRIL silencing exerted anti-apoptotic and anti-inflammatory effects by positively regulating the expression of miR-622. Furthermore, inhibition of OGD/R-induced activation of the nuclear factor (NF)-kB pathway by circ_ANRIL silencing was significantly reversed by treatment with miR-622 inhibitor. CONCLUSIONS: Knockdown of circ_ANRIL improved OGD/R-induced cell damage, apoptosis, and inflammatory responses by inhibiting the NF-κB pathway through sponging miR-622.

Humans , Reperfusion Injury/metabolism , Hypoxia, Brain/metabolism , MicroRNAs/physiology , MicroRNAs/genetics , RNA, Circular , Oxygen , Brain , Apoptosis , Cyclin-Dependent Kinase Inhibitor p16 , Endothelial Cells , RNA, Long Noncoding , Glucose/metabolism , Inflammation
Arch. endocrinol. metab. (Online) ; 63(6): 582-591, Nov.-Dec. 2019. tab
Article in English | LILACS | ID: biblio-1055018


ABSTRACT GH is one of the insulin counterregulatory hormones which acts in the opposite way to insulin, increasing the glucose production by the liver and kidneys and decreasing glucose uptake from peripheral tissues, thus being a hyperglycemic hormone. When in excess, as in acromegaly, it induces glucose intolerance and diabetes. As expected, patients with GH deficiency (GHD) have hypoglycemia, especially in early childhood, but as GH is also a lipolytic hormone, these patients are becoming obese with higher percentages of body fat. Although obesity in general is directly related to insulin resistance, in patients with GH secretion disorders this relationship may be altered. In acromegaly there is a decrease in fat mass with worsening insulin sensitivity and mice with isolated GHD are characterized by greater insulin sensitivity despite excess fat mass. In humans with GHD, body composition shows increased body fat and decreased free fat mass, but the results regarding insulin sensitivity are still controversial in these patients. These discrepant results regarding insulin sensitivity in patients with GHD suggest the existence of other variables influencing these results. In the present review, we will try to follow the path of the different researches conducted on this subject, both in animal and human models, with the goal of understanding the current knowledge of insulin sensitivity across the spectrum of GHD. Arch Endocrinol Metab. 2019;63(6):582-91

Humans , Animals , Insulin Resistance/physiology , Signal Transduction/physiology , Human Growth Hormone/deficiency , Human Growth Hormone/physiology , Glucose/physiology , Glucose/metabolism
Arch. endocrinol. metab. (Online) ; 63(4): 376-384, July-Aug. 2019. tab
Article in English | LILACS | ID: biblio-1019349


ABSTRACT Objective To test the influence of oral fructose and glucose dose-response solutions in blood glucose (BG), glucagon, triglycerides, uricaemia, and malondialdehyde in postprandial states in type 1 diabetes mellitus (T1DM) patients. Subjects and methods The study had a simple-blind, randomized, two-way crossover design in which T1DM patients were selected to receive fructose and glucose solutions (75g of sugars dissolved in 200 mL of mineral-water) in two separate study days, with 2-7 weeks washout period. In each day, blood samples were drawn after 8h fasting and at 180 min postprandial to obtain glucose, glucagon, triglycerides, uric acid, lactate, and malondialdehyde levels. Results Sixteen T1DM patients (seven men) were evaluated, with a mean age of 25.19 ± 8.8 years, a mean duration of disease of 14.88 ± 4.73 years, and glycated hemoglobin of 8.13 ± 1.84%. Fructose resulted in lower postprandial BG levels than glucose (4.4 ± 5.5 mmol/L; and 12.9 ± 4.1 mmol/L, respectively; p < 0.01). Uric acid levels increased after fructose (26.1 ± 49.9 µmol/L; p < 0.01) and reduced after glucose (-13.6 ± 9.5 µmol/L; p < 0.01). The malondialdehyde increased after fructose (1.4 ± 1.6 µmol/L; p < 0.01) and did not change after glucose solution (-0.2 ± 1.6 µmol/L; p = 0.40). Other variables did not change. Conclusions Fructose and glucose had similar sweetness, flavor and aftertaste characteristics and did not change triglycerides, lactate or glucagon levels. Although fructose resulted in lower postprandial BG than glucose, it increased uric acid and malondialdehyde levels in T1DM patients. Therefore it should be used with caution. registration: NCT01713023.

Humans , Male , Female , Adolescent , Adult , Middle Aged , Young Adult , Sweetening Agents/metabolism , Postprandial Period/drug effects , Diabetes Mellitus, Type 1/metabolism , Fructose/metabolism , Glucose/metabolism , Triglycerides/blood , Blood Glucose/analysis , Blood Glucose/drug effects , Cross-Over Studies , Dose-Response Relationship, Drug , Drug Tolerance
Medicina (B.Aires) ; 79(2): 137-143, abr. 2019. tab
Article in Spanish | LILACS | ID: biblio-1002619


La cocción de los alimentos a altas temperaturas en calor seco, produce ciertas modificaciones organolépticas que los hace especialmente apetecibles y objetos de adicción. Esto es resultado de la reacción de Maillard, o glicación, que se produce por unión no enzimática del grupo carbonilo, de azúcares reductores como glucosa y fructosa, con el grupo amino de proteínas y ácidos nucleicos. Junto a los cambios físicos, cambia la estructura química y la función de estos aductos, denominados también glicotoxinas. Además de la glicación exógena, generada durante la cocción de los alimentos, recientemente ha sido referida la glicación in situ, en la luz intestinal, durante la digestión, cuando determinados alimentos no glicados se combinan en el momento de su ingestión. A esto se agrega la glicación endógena extracelular relacionada con la glucosa sanguínea y la intracelular, con metabolitos de la glucólisis y de la fructosa. Desde la década del 70, con el remplazo en gran medida de la sacarosa por fructosa, significativamente más reactiva que la glucosa, aumentó la presencia de productos de glicación en alimentos procesados y bebidas gaseosas. Están documentados sus efectos patogénicos como contribuyentes al estrés oxidativo y a la inflamación, especialmente en diabetes, insuficiencia renal y enfermedad cardiovascular y están siendo explorados en otras enfermedades crónicas, como procesos neurodegenerativos y envejecimiento temprano. Se describen medidas para preservar la salud, atendiendo medios de cocción y procesamiento de los alimentos y recomendaciones sobre hábitos de vida e ingesta de antioxidantes para acción inhibitoria o antagónica sobre las glicotoxinas.

Certain organoleptic modifications by way of processing and cooking foods at high temperatures in dry heat, make them especially appetizing and objects of addiction. It results from Maillard reaction, or glycation, consisting of the non-enzymatic union between carbonyl groups, mainly from reducing sugars as glucose and fructose, with the amino group of proteins and nucleic acids. In addition to physical changes, also the chemical structure and function of these compounds are changed. Besides exogenous glycation generated during the cooking of foods, recently in situ glycation has been reported in the intestinal lumen during digestion, when certain non-glycated foods are combined with fructose at the time of ingestion. In addition, endogenous glycation, which correlates in the extracellular mainly with blood glucose and in the intracellular with glycolysis metabolites and fructose, is specially significant. Since the 70s, with the frequent sucrose replacement by fructose, much more reactive than glucose, the presence of glycation products in processed foods and soft drinks increased.Pathogenic effects of these compounds, also called glycotoxins, are known to contribute to oxidative stress and inflammation. This increases progression of chronic diseases, well documented in diabetes, renal insuficiency, cardiovascular disease and aging process, and are being explore d in many other chronic diseases as neurodegenerative disorders and early aging. Based on the knowledge achieved so far, measures to preserve health are described by attending ways of cooking and processing foods, besides recommendations for life habits and antioxidants dietary intakes for inhibition or antagonism on glycotoxins.

Humans , Maillard Reaction , Glycation End Products, Advanced/metabolism , Food , Risk Factors , Glycation End Products, Advanced/chemistry , Oxidative Stress/physiology , Fructose/metabolism , Glucose/metabolism
Braz. j. med. biol. res ; 52(2): e7637, 2019. tab, graf
Article in English | LILACS | ID: biblio-984028


Non-diabetic individuals use hormones like insulin to improve muscle strength and performance. However, as insulin also leads the liver and the adipose tissue to an anabolic state, the purpose of this study was to investigate the effects of insulin on liver metabolism in trained non-diabetic Swiss mice. The mice were divided into four groups: sedentary treated with saline (SS) or insulin (SI) and trained treated with saline (TS) or insulin (TI). Training was made in a vertical stair, at 90% of the maximum load, three times per week. Insulin (0.3 U/kg body weight) or saline were given intraperitoneally five times per week. After eight weeks, tissue and blood were collected and in situ liver perfusion with glycerol+lactate or alanine+glutamine (4 mM each) was carried out. The trained animals increased their muscle strength (+100%) and decreased body weight gain (-11%), subcutaneous fat (-42%), mesenteric fat (-45%), and peritoneal adipocyte size (-33%) compared with the sedentary groups. Insulin prevented the adipose effects of training (TI). The gastrocnemius muscle had greater density of muscle fibers (+60%) and less connective tissue in the trained groups. Liver glycogen was increased by insulin (SI +40% and TI +117%), as well as liver basal glucose release (TI +40%). Lactate and pyruvate release were reduced to a half by training. The greater gluconeogenesis from alanine+glutamine induced by training (TS +50%) was reversed by insulin (TI). Insulin administration had no additional effect on muscle strength and reversed some of the lipolytic and gluconeogenic effects of the resistance training. Therefore, insulin administration does not complement training in improving liver glucose metabolism.

Animals , Male , Rabbits , Physical Conditioning, Animal/physiology , Muscle Strength , Glucose/administration & dosage , Glucose/adverse effects , Liver/drug effects , Exercise Test , Resistance Training , Glucose/metabolism , Liver/metabolism
Clinics ; 74: e1273, 2019. tab, graf
Article in English | LILACS | ID: biblio-1039567


OBJECTIVES: This study aimed to evaluate several methods to estimate glucose consumption in the male Wister rat brain as measured by PET. METHODS: Fourteen male Wistar normoglycemic rats were studied. The input function consisted of seventeen blood samples drawn manually from the femoral artery. Glucose uptake values were calculated using the input function resulting from the arterial blood samples and the tissue time-activity curve derived from the PET images. The estimated glucose consumption rate (Ki) based on the 2-tissue compartment model (2TCM) served as the standard for comparisons with the values calculated by the Patlak analysis and with the fractional uptake rate (FUR), standardized uptake value (SUV) and glucose corrected SUV (SUVglu). RESULTS: No significant difference between the standard Ki and the Patlak Ki was observed. The standard Ki was also found to have strong correlations and concordance with the Ki value estimated by the Patlak analysis. The FUR method presented an excellent correlation with the Ki value obtained by the 2TCM/Patlak analyses, in contrast to the SUV or SUVglu. CONCLUSIONS: From a methodological point of view, the present findings confirm the theoretical limitations of the cerebral SUV and SUVglu as a substitute for Ki in the estimation of glucose consumption in the brain. Our data suggest that the FUR is the surrogate to Ki.

Animals , Male , Rats , Brain/metabolism , Brain/diagnostic imaging , Fluorodeoxyglucose F18/administration & dosage , Positron-Emission Tomography/methods , Glucose/metabolism , Rats, Wistar , Models, Animal
Rev. chil. endocrinol. diabetes ; 12(4): 208-215, 2019. tab, ilus
Article in Spanish | LILACS | ID: biblio-1088029


INTRODUCCIÓN: Si bien, los edulcorantes no nutritivos (ENN) estevia y D-tagatosa han sido reportados como seguros, han demostrado tener algunos efectos metabólicos tras su ingesta. OBJETIVO: Describir los efectos de la ingesta de estevia y D-tagatosa sobre el metabolismo de la glucosa y ácido úrico, y del apetito-saciedad, a partir de la evidencia disponible. MÉTODOS: Revisión descriptiva. Se realizó búsqueda en PubMed utilizando los siguientes términos y palabras clave: "stevia rebaudiana", "tagatose", "D-tagatose", "blood glucose", "insulin", "metabolic processes", "uric acid", "hyperuricemia", "appetite" o "satiety". El análisis de los estudios seleccionados fue discrecional. RESULTADOS: Existen estudios que demuestran efectos beneficiosos tras el consumo de estevia o D-tagatosa sobre el control glicémico, apetito y saciedad tanto en sujetos sanos como con alteraciones en el metabolismo de la glucosa. Por otra parte, un número importante de estudios que evalúan la ingesta de estevia reportan efectos nulos sobre dichos parámetros. En relación al ácido úrico, solo un estudio en sujetos con enfermedad renal crónica reporta aumento en la concentración de ácido úrico plasmático tras la ingesta de 500 mg/día de estevia. Pocos estudios han evaluado el efecto de la ingesta de D-tagatosa sobre uricemia, en sujetos sanos y diabéticos, reportando un aumento transitorio y significativo en los niveles de ácido úrico sérico, sin embargo, no se ha logrado demostrar un efecto hiperuricémico asociado. Es importante destacar que la metodología de los estudios revisados es heterogénea, especialmente en relación al tamaño muestral, tiempo, dosis y vía de adminitración del edulcorante. CONCLUSIÓN: La ingesta de estevia y D-tagatosa ha demostrado efectos beneficiosos sobre el metabolismo de la glucosa, el apetito y la saciedad. El efecto del consumo de D-tagatosa sobre ácido úrico sérico requiere mayor evidencia para demostrar su significancia clínica.

INTRODUCTION: No-nutritive sweeteners stevia and D-tagatose have been reported as safe according to their acceptable daily intake, however, they have been shown to have metabolic effects after their ingestion. OBJECTIVE: To describe the effects of stevia and D-tagatose intake on parameters associated to glucose, uric acid metabolism and on appetite-satiety, considering the available evidence. METHODS: Descriptive review. PubMed search was carried out to identify the totality of the published articles. The following terms and key words were used: "stevia rebaudiana", "tagatose", "D-tagatose", "blood glucose", "insulin", "metabolic processes", "uric acid", "hyperuricemia", "appetite" o "satiety". The analysis of the selected studies was discretionary. RESULTS: studies have shown beneficial effects of stevia and D-tagatose consumption on glycemic control, appetite and satiety in healthy subjects as well as subjects with impairment glucose metabolism. On the other hand, a significant number of studies evaluating estevia intake report null effects on these parameters. In relation to uric acid, only one study in subjects with chronic kidney disease reported an increase in plasmatic uric acid concentration after the intake of 500 mg/day of stevia. Several studies have evaluated the effect of D-tagatose intake on plasmatic uric acid, in healthy and diabetic subjects, reporting a transient and significant increase in serum uric acid levels, however, has not been able to demonstrate an associated hyperuricemic effect. It is important to highlight that the methodology of the studies reviewed is heterogeneous, especially in relation to sample size, dose administered, time and route of exposure to the sweetener. CONCLUSION: Stevia and D-tagatose intake has shown beneficial effects on glucose metabolism, appetite and satiety. The effects of the consumption of both sweeteners on uric acid require further study to demonstrate their clinic significance.

Humans , Sweetening Agents/pharmacology , Uric Acid/metabolism , Blood Glucose/drug effects , Appetite/drug effects , Satiation/drug effects , Stevia/metabolism , Glucose/metabolism , Hexoses/pharmacology , Insulin/metabolism
Braz. j. microbiol ; 49(4): 865-871, Oct.-Dec. 2018. tab, graf
Article in English | LILACS | ID: biblio-974297


ABSTRACT The ability of four Aspergillus strains for biosynthesis of kojic acid was evaluated among which Aspergillus terreus represented the highest level (2.21 g/L) of kojic acid production. Improvement kojic acid production ability of A. terreus by random mutagenesis using different exposure time to ultraviolet light (5-40 min) was then performed to obtain a suitable mutant of kojic acid production (designated as C5-10, 7.63 g/L). Thereafter, design of experiment protocol was employed to find medium components (glucose, yeast extract, KH2PO4 (NH4)2SO4, and pH) influences on kojic acid production by the C5-10 mutant. A 25-1 fractional factorial design augmented to central composite design showed that glucose, yeast extract, and KH2PO4 were the most considerable factors within the tested levels (p < 0.05). The optimum medium composition for the kojic acid production by the C5-10 mutant was found to be glucose, 98.4 g/L; yeast extract, 1.0 g/L; and KH2PO4, 10.3 mM which was theoretically able to produce 120.2 g/L of kojic acid based on the obtained response surface model for medium optimization. Using these medium compositions an experimental maximum Kojic acid production (109.0 ± 10 g/L) was acquired which verified the efficiency of the applied method.

Pyrones/metabolism , Aspergillus/radiation effects , Aspergillus/metabolism , Aspergillus/growth & development , Aspergillus/genetics , Ultraviolet Rays , Mutagenesis , Culture Media/metabolism , Fermentation , Glucose/metabolism
Rev. bras. parasitol. vet ; 27(3): 259-266, July-Sept. 2018. tab, graf
Article in English | LILACS | ID: biblio-959194


Abstract The cattle tick Rhipicephalus (Boophilus) microplus is an ectoparasite capable of transmitting a large number of pathogens, causing considerable losses in the cattle industry, with substantial damage to livestock. Over the years, important stages of its life cycle, such as the embryo, have been largely ignored by researchers. Tick embryogenesis has been typically described as an energy-consuming process, sustaining cell proliferation, differentiation, and growth. During the embryonic stage of arthropods, there is mobilization of metabolites of maternal origin for the development of organs and tissues of the embryo. Glycogen resynthesis in late embryogenesis is considered as an effective indicator of embryonic integrity. In the cattle tick R.(B. (B.) microplus, glycogen resynthesis is sustained by protein degradation through the gluconeogenesis pathway at the end of the embryonic period. Despite recent advancements in research on tick energy metabolism at the molecular level, the dynamics of nutrient utilization during R. (B.) microplus embryogenesis is still poorly understood. The present review aims to describe the regulatory mechanisms of carbohydrate metabolism during maternal-zygotic transition and identify possible new targets for the development of novel drugs and other control measures against R. (B.) microplus infestations.

Resumo O carrapato bovino Rhipicephalus (B.) microplus é um ectoparasita capaz de transmitir diversos patógenos, sendo responsável por grandes perdas na pecuária pelos danos causados ao gado. Atualmente, muitos estudos têm negligenciado fases importantes do ciclo de vida deste parasita, como a fase embrionária. A embriogênese é classicamente descrita como um processo que demanda um consumo de energia, possibilitando a proliferação celular, diferenciação e crescimento. Além disso, em artrópodes, o estágio da embriogênese é caracterizado pela mobilização de metabolitos de origem materna para o desenvolvimento de novos tecidos e órgãos. A ressíntese de glicogênio no final da embriogênese tem sido descrita em diversas espécies de artrópodes, sendo considerada um indicador de integridade do embrião. No caso do R. (B.) microplus a ressíntese de glicogênio é sustentada pela degradação de proteínas durante a gliconeogênese, no terço final da embriogênese. Apesar dos recentes avanços, no estudo molecular e do metabolismo energético, os mecanismos envolvidos na dinâmica da utilização de diferentes substratos energéticos durante a embriogênese do carrapato R. (B.) microplus ainda é pouco entendido. Diante deste panorama, estudos que descrevam a regulação destes mecanismos e da associação do metabolismo de carboidratos com a transição materno zigótica, pode auxiliar na busca de novos alvos para o desenvolvimento de novos acaricidas e outras intervenções para o controle infestações de R. (B.) microplus.

Animals , Rhipicephalus/embryology , Embryo, Nonmammalian/metabolism , Energy Metabolism/physiology , Gluconeogenesis/physiology , Glucose/metabolism , Rhipicephalus/metabolism
Braz. j. microbiol ; 49(2): 258-268, Apr.-June 2018. graf
Article in English | LILACS | ID: biblio-889233


Abstract Cellulosimicrobium cellulans CWS2, a novel strain capable of utilizing benzo(a)pyrene (BaP) as the sole carbon and energy source under nitrate-reducing conditions, was isolated from PAH-contaminated soil. Temperature and pH significantly affected BaP biodegradation, and the strain exhibited enhanced biodegradation ability at temperatures above 30 °C and between pH 7 and 10. The highest BaP removal rate (78.8%) was observed in 13 days when the initial BaP concentration was 10 mg/L, and the strain degraded BaP at constant rate even at a higher concentration (50 mg/L). Metal exposure experimental results illustrated that Cd(II) was the only metal ion that significantly inhibited biodegradation of BaP. The addition of 0.5 and 1.0 g/L glucose enhanced BaP biodegradation, while the addition of low-molecular-weight organic acids with stronger acidity reduced BaP removal rates during co-metabolic biodegradation. The addition of phenanthrene and pyrene, which were degraded to some extent by the strain, showed no distinct effect on BaP biodegradation. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that the five rings of BaP opened, producing compounds with one to four rings which were more bioavailable. Thus, the strain exhibited strong BaP degradation capability and has great potential in the remediation of BaP-/PAH-contaminated environments.

Soil Microbiology , Soil Pollutants/metabolism , Benzo(a)pyrene/metabolism , Actinobacteria/isolation & purification , Actinobacteria/metabolism , Temperature , Cadmium/metabolism , Carbon/metabolism , Carboxylic Acids/metabolism , Biotransformation , Actinobacteria/classification , Culture Media/chemistry , Enzyme Inhibitors/metabolism , Glucose/metabolism , Hydrogen-Ion Concentration , Anaerobiosis , Gas Chromatography-Mass Spectrometry
Rev. méd. Chile ; 146(4): 502-510, abr. 2018. tab, graf
Article in Spanish | LILACS | ID: biblio-961421


Stress hyperglycemia is frequently diagnosed in septic patients in critical care units (ICU) and it is associated with greater illness severity and higher morbimortality rates. In response to an acute injury, high levels of counterregulatory hormones such as glucocorticoids and catecholamines are released causing increased hepatic gluconeogenesis and insulin resistance. Furthermore, during sepsis, proinflammatory cytokines also participate in the pathogenesis of this phenomenon. Septic patients represent a subtype of the critical ill patients in the ICU: this metabolic disarrangement management strategies and insulin therapy recommendations had been inconsistent. In this article, we describe the pathophysiological mechanisms of stress hyperglycemia in critical patients including the action of hormones, inflammatory cytokines and tissue resistance to insulin. In addition, we analyzed the main published studies for the treatment of acute hyperglycemia in critical patients.

Humans , Sepsis/complications , Hyperglycemia/etiology , Stress, Physiological , Sepsis/physiopathology , Sepsis/metabolism , Glucose Transport Proteins, Facilitative/metabolism , Glucose/metabolism , Hyperglycemia/physiopathology , Hyperglycemia/metabolism , Hyperglycemia/therapy , Intensive Care Units
São Paulo; s.n; 2018. 81 p.
Thesis in Portuguese | LILACS | ID: biblio-947265


Introdução: Especula-se que exista uma possível relação entre a ingestão de vitamina K e a diminuição da gordura corporal. Além disso, embora os resultados permaneçam controversos, há um número crescente de estudos que apoiam um papel chave dessa vitamina na melhora do perfil lipídico, da sensibilidade à insulina e na redução do risco de diabetes mellitus tipo 2, contudo pouco se sabe sobre quais mecanismos estariam envolvidos. Objetivo: Investigar as relações entre a ingestão de vitamina K (na forma de filoquinona - PK), gordura corporal, perfil lipídico e marcadores da homeostase da glicose em adultos e idosos. Métodos: Estudo transversal com 298 indivíduos de ambos os sexos, participantes do inquérito ISA - Capital 2015. Amostras de sangue foram coletadas para determinação do perfil lipídico, glicemia de jejum e concentrações de insulina; e índice de estimativa de resistência à insulina (HOMAIR), índice de estimativa da função de células β-pancreáticas (HOMA-β) e índice de estimativa da sensibilidade à insulina (QUICKI) foram calculados. A ingestão de vitamina K foi avaliada por meio de um recordatório alimentar de 24hrs (repetido em 75% da amostra), e a investigação quantitativa da massa gorda foi conduzida por meio da absorciometria de feixe duplo (DXA). Indivíduos com ingestão de vitamina K inferior aos valores de AI foram divididos em subgrupos de acordo com o estado nutricional e faixa etária. Foi realizada a Correlação de Spearman em grupos estratificados de acordo com o Índice de Massa Corporal (IMC) e com o Índice de Gordura Corporal (IGC). Para avaliar as associações entre a ingestão de vitamina K e cada uma das medidas bioquímicas e de adiposidade, foi realizada a regressão linear múltipla. Resultados: Dentre os avaliados, 46% eram do sexo masculino (n=136), com idade mediana de 61 anos (20 - 94 anos), e 56,4% apresentavam sobrepeso ou obesidade (n=168). A mediana de ingestão de vitamina K foi de 102,7 μg, ou 59,9 μg,/1000 kcal, sem diferença de acordo com sexo ou idade. A ingestão de vitamina K apresentou correlação negativa com o HOMA-IR (r = -0,603; p = 0,0134) e correlação positiva com QUICKI (r = 0,603; p = 0,0134) entre os adultos eutróficos do sexo masculino (n = 16). Em idosas com baixo peso (n = 12), a ingestão de vitamina K foi negativamente correlacionada com o Colesterol Total (CT) (r = -0,644; p = 0,0443). Entre as mulheres com elevado IGC e ingestão de vitamina K inferior aos valores de AI (n = 117), foram observadas correlações negativas entre a ingestão de vitamina K e HOMA-IR (r = -0,187; p = 0,0451) e correlações positivas com QUICKI (r = 0,187; p = 0,0451). Conclusões: Os resultados encontrados sugerem uma possível relação entre a ingestão dietética de filoquinona, gordura corporal, perfil lipídico e marcadores da homeostase da glicose, em amostra de adultos e idosos

Introduction: Recent research have investigated a possible inverse relationship between vitamin K intake and body fat. In addition, although the results remain controversial, there is an increasing number of studies supporting a key role of this vitamin in improving lipid profile, insulin sensitivity and reducing the risk of type 2 diabetes mellitus, but little is known about what mechanisms would be involved. Objective: To investigate the relationship between vitamin K intake (in the form of phylloquinone - PK), body fat, lipid profile and markers of glucose homeostasis in adults and elderly. Methods: Cross-sectional study with 298 individuals of both sexes, participants in the ISA - Capital 2015 survey. Blood samples were collected for determination of lipid profile, fasting glycemia and insulin concentrations, and homeostasis model assesment estimate for insulin resistance (HOMA-IR), homeostasis model assessment estimate for β-cell function (HOMA-β) and the quantitative insulin sensitivity check index (QUICKI) were calculate accordingly. Vitamin K intake was assessed by a 24-hour dietary recall (repeated in 75% of the sample) and quantitative investigation of fat mass was conducted using dual-energy x-ray absorptiometry (DXA). Subjects with vitamin K intake lower than AI values were divided into subgroups according to nutritional status and age group. Spearman correlation was performed in stratified groups according to Body Mass Index (BMI) and Fat Mass Index (FMI). To evaluate the associations between vitamin K intake and each of the biochemical and adiposity measures, multiple linear regression were performed. Results: Among the sample, 46% were male (n = 136), with a median age of 61 years (20 - 94 years), and 56.4% were overweight or obese (n= 168). The median vitamin K intake was 102.7 μg, or 59.9 μg, / 1000 kcal, with no difference according to sex or age. Vitamin K intake presented negative correlation with HOMA-IR (r = -0.603; p = 0.0134) and positive correlation with QUICKI (r = 0.603; p=0.0134) among normal weight male adults (n=16). In underweight elderly women (n=12), vitamin K intake was negatively correlated with total cholesterol (TC) (r = -0.644, p = 0.0443). Among females with high FMI and vitamin K intake lower than AI values (n=117), vitamin K intake was negatively correlated with HOMA-IR (r = -0.187; p = 0.0451) and positively correlated with QUICKI (r 12 = 0.187; p = 0.0451). Conclusions: Results suggest a possible relationship between dietary intake of phylloquinone, body fat, lipid profile and glucose homeostasis, among a sample of adults and elderly

Humans , Adult , Aged , Adiposity , Glucose/metabolism , Homeostasis , Lipids/blood , Vitamin K 1 , Cross-Sectional Studies
Braz. j. microbiol ; 49(supl.1): 160-165, 2018. tab, graf
Article in English | LILACS | ID: biblio-974323


Abstract Sclareol is an important intermediate for ambroxide synthesis industries. Hyphozyma roseonigra ATCC 20624 was the only reported strain capable of degrading sclareol to the main product of sclareol glycol, which is the precursor of ambroxide. To date, knowledge is lacking about the effects of sclareol on cells and the proteins involved in sclareol metabolism. Comparative proteomic analyses were conducted on the strain H. roseonigra ATCC 20624 by using sclareol or glucose as the sole carbon source. A total of 79 up-regulated protein spots with a >2.0-fold difference in abundance on 2-D gels under sclareol stress conditions were collected for further identification. Seventy spots were successfully identified and finally integrated into 30 proteins. The up-regulated proteins under sclareol stress are involved in carbon metabolism; and nitrogen metabolism; and replication, transcription, and translation processes. Eighteen up-regulated spots were identified as aldehyde dehydrogenases, which indicating that aldehyde dehydrogenases might play an important role in sclareol metabolism. Overall, this study may lay the fundamentals for further cell engineering to improve sclareol glycol production.

Ascomycota/metabolism , Fungal Proteins/metabolism , Diterpenes/metabolism , Ascomycota/genetics , Ascomycota/chemistry , Fungal Proteins/chemistry , Carbon/metabolism , Electrophoresis, Gel, Two-Dimensional , Gene Expression Regulation, Fungal , Proteomics , Glucose/metabolism
Biol. Res ; 51: 35, 2018. graf
Article in English | LILACS | ID: biblio-983939


BACKGROUND: The previous studies have demonstrated the reduction of thiamine diphosphate is specific to Alzheimer's disease (AD) and causal factor of brain glucose hypometabolism, which is considered as a neurodegenerative index of AD and closely correlates with the degree of cognitive impairment. The reduction of thiamine diphosphate may contribute to the dysfunction of synapses and neural circuits, finally leading to cognitive decline. RESULTS: To demonstrate this hypothesis, we established abnormalities in the glucose metabolism utilizing thiamine deficiency in vitro and in vivo, and we found dramatically reduced dendrite spine density. We further detected lowered excitatory neurotransmission and impaired hippocampal long-term potentiation, which are induced by TPK RNAi in vitro. Importantly, via treatment with benfotiamine, Aß induced spines density decrease was considerably ameliorated. CONCLUSIONS: These results revealed that thiamine deficiency contributed to synaptic dysfunction which strongly related to AD pathogenesis. Our results provide new insights into pathogenesis of synaptic and neuronal dysfunction in AD.

Animals , Male , Synapses/physiology , Thiamine Deficiency/complications , Thiamine Deficiency/metabolism , Thiamine Pyrophosphate/deficiency , Alzheimer Disease/etiology , Alzheimer Disease/metabolism , Neurons/physiology , Thiamine Deficiency/physiopathology , Thiamine Pyrophosphate/metabolism , Random Allocation , Blotting, Western , Amyloid beta-Peptides/metabolism , Rats, Sprague-Dawley , Diphosphotransferases/metabolism , Synaptic Transmission/physiology , Dendritic Spines/metabolism , Alzheimer Disease/physiopathology , Real-Time Polymerase Chain Reaction , Glucose/metabolism , Hippocampus/physiopathology , Hippocampus/metabolism , Mice, Inbred C57BL
Braz. j. med. biol. res ; 51(1): e6724, 2018. tab, graf
Article in English | LILACS | ID: biblio-889005


Basal ganglia have complex functional connections with the cerebral cortex and are involved in motor control, executive functions of the forebrain, such as the planning of movement, and cognitive behaviors based on their connections. The aim of this study was to provide detailed functional correlation patterns between the basal ganglia and cerebral cortex by conducting an interregional correlation analysis of the 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) data based on precise structural information. Fifteen participants were scanned with 7-Tesla magnetic resonance imaging (MRI) and high resolution research tomography (HRRT)-PET fusion system using 18F-FDG. For detailed interregional correlation analysis, 24 subregions of the basal ganglia including pre-commissural dorsal caudate, post-commissural caudate, pre-commissural dorsal putamen, post-commissural putamen, internal globus pallidus, and external globus pallidus and 80 cerebral regions were selected as regions of interest on the MRI image and their glucose metabolism were calculated from the PET images. Pearson's product-moment correlation analysis was conducted for the interregional correlation analysis of the basal ganglia. Functional correlation patterns between the basal ganglia and cerebral cortex were not only consistent with the findings of previous studies, but also showed new functional correlation between the dorsal striatum (i.e., caudate nucleus and putamen) and insula. In this study, we established the detailed basal ganglia subregional functional correlation patterns using 18F-FDG PET/MRI fusion imaging. Our methods and results could potentially be an important resource for investigating basal ganglia dysfunction as well as for conducting functional studies in the context of movement and psychiatric disorders.

Humans , Male , Female , Adult , Young Adult , Basal Ganglia/diagnostic imaging , Magnetic Resonance Imaging/methods , Cerebral Cortex/diagnostic imaging , Fluorodeoxyglucose F18 , Positron-Emission Tomography/methods , Glucose/metabolism , Reference Standards , Basal Ganglia/metabolism , Cerebral Cortex/metabolism , Reproducibility of Results , Radiopharmaceuticals
Braz. j. microbiol ; 48(4): 791-800, Oct.-Dec. 2017. graf
Article in English | LILACS | ID: biblio-889166


ABSTRACT Lignocellulose-derived inhibitors have negative effects on the ethanol fermentation capacity of Saccharomyces cerevisiae. In this study, the effects of eight typical inhibitors, including weak acids, furans, and phenols, on glucose and xylose co-fermentation of the recombinant xylose-fermenting flocculating industrial S. cerevisiae strain NAPX37 were evaluated by batch fermentation. Inhibition on glucose fermentation, not that on xylose fermentation, correlated with delayed cell growth. The weak acids and the phenols showed additive effects. The effect of inhibitors on glucose fermentation was as follows (from strongest to weakest): vanillin > phenol > syringaldehyde > 5-HMF > furfural > levulinic acid > acetic acid > formic acid. The effect of inhibitors on xylose fermentation was as follows (from strongest to weakest): phenol > vanillin > syringaldehyde > furfural > 5-HMF > formic acid > levulinic acid > acetic acid. The NAPX37 strain showed substantial tolerance to typical inhibitors and showed good fermentation characteristics, when a medium with inhibitor cocktail or rape straw hydrolysate was used. This research provides important clues for inhibitors tolerance of recombinant industrial xylose-fermenting S. cerevisiae.

Saccharomyces cerevisiae/drug effects , Xylose/metabolism , Glucose/metabolism , Phenols/metabolism , Phenols/pharmacology , Saccharomyces cerevisiae/growth & development , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Acids/metabolism , Acids/pharmacology , Industrial Microbiology , Fermentation , Furans/metabolism , Furans/pharmacology
Actual. osteol ; 13(3): 225-232, Sept - DIc. 2017. ilus
Article in Spanish | LILACS | ID: biblio-1117386


El esqueleto es uno de los sistemas más grandes de un vertebrado y, como tal, es razonable especular que no puede funcionar aislado del resto del organismo. De hecho, sabemos que existen sistemas complejos de regulación cruzada entre el esqueleto y muchos otros órganos. Hoy poseemos herramientas que nos permiten realizar supresión genética en células o tejidos específicos. Esto nos ha permitido comprender cómo los órganos se comunican entre sí y ha revitalizado el concepto de fisiología del organismo como un todo. Efectivamente, los últimos años han sido testigos del descubrimiento de funciones inesperadas que ejerce el esqueleto y que afectan al organismo en su totalidad. Una de tales funciones reconocidas recientemente es el control del metabolismo energético, a través de la secreción de osteocalcina. La osteocalcina es una hormona producida por los osteoblastos que regula la secreción de insulina, la sensibilidad a esta hormona y el metabolismo energético. Los hallazgos iniciales suscitaron varias preguntas fundamentales sobre la naturaleza de la acción de la insulina sobre el hueso. Pero esto solo fue la punta del iceberg. Efectivamente, más adelante se descubrió, mediante el análisis de ratones que carecen del receptor de insulina (Ins R) solamente en osteoblastos, que la acción de la insulina sobre estas células favorecía la homeostasis de la glucosa en todo el cuerpo. Es importante destacar que esta función de la insulina en los osteoblastos opera mediante la regulación negativa de la carboxilación y la biodisponibilidad de la osteocalcina. Más aún, se observó que las vías de señalización de la insulina en los osteoblastos regulan positivamente no solo la formación sino también la resorción del hueso. Curiosamente, parece que las vías de señalización de la insulina en osteoblastos pueden inducir la activación de la osteocalcina mediante la estimulación de la actividad de los osteoclastos. De hecho, el bajo pH generado durante la resorción ósea es suficiente para desencadenar la descarboxilación (y subsiguiente activación) de la osteocalcina. En breve discutiremos dos nuevas proposiciones: 1) los osteoblastos son un blanco utilizado por la insulina para controlar la homeostasis de la glucosa en todo el organismo y 2) la resorción ósea desempeña un papel fundamental en la regulación de la activación de la osteocalcina. (AU)

The skeleton is one of the biggest systems in a vertebrate animal and, as such, it is reasonable to speculate that it cannot function isolated from the rest of the organism. In fact, we know that complex systems exist for the cross-regulation between the skeleton and several other organs. Today, we have the tools that allow us to perform genetic suppression in specific cells or tissues. This has allow us understand the mechanisms by which the organs communicate with each other and has revitalized the concept of organismal physiology as a whole. Studies conducted in recent years have uncovered unexpected functions performed by the skeleton. One of these is the control of global energy metabolism, through the secretion of osteocalcin, a protein produced by osteoblasts that acts as a hormone regulating insulin secretion, insulin sensitivity and energy expenditure. The evidence comes from the analysis of mice lacking insulin receptor (InsR) exclusively in osteoblasts. These mice have a global metabolic phenotype demonstrating that the action of insulin in osteoblasts promotes the homeostasis of glucose throughout the body. This action of insulin in osteoblasts is mediated by the negative regulation of the carboxylation (and bioavailability) of osteocalcin. The decarboxylation (and activation) of osteocalcin, in turn, occurs in the osteoclastic resorption pit. Briefly: the osteoblast is a target used by insulin to control the homeostasis of glucose throughout the body and bone resorption is the mechanism that regulates the activation of osteocalcin. (AU)

Humans , Animals , Mice , Osteocalcin/biosynthesis , Energy Metabolism , Insulin/biosynthesis , Osteoblasts/metabolism , Osteogenesis , Skeleton/physiology , Skeleton/metabolism , Bone Resorption/metabolism , Receptor, Insulin/metabolism , Signal Transduction , Osteocalcin/metabolism , Decarboxylation , Insulin Secretion , Glucose/biosynthesis , Glucose/metabolism , Insulin/metabolism