Glucose Transport and Utilization in the Hippocampus: From Neurophysiology to Diabetes-Related Development of Dementia.

The association of diabetes with cognitive dysfunction has at least 60 years of history, which started with the observation that children with type 1 diabetes mellitus (T1D), who had recurrent episodes of hypoglycemia and consequently low glucose supply to the brain, showed a deficit of cognitive capacity. Later, the growing incidence of type 2 diabetes mellitus (T2D) and dementia in aged populations revealed their high association, in which a reduced neuronal glucose supply has also been considered as a key mechanism, despite hyperglycemia. Here, we discuss the role of glucose in neuronal functioning/preservation, and how peripheral blood glucose accesses the neuronal intracellular compartment, including the exquisite glucose flux across the blood-brain barrier (BBB) and the complex network of glucose transporters, in dementia-related areas such as the hippocampus. In addition, insulin resistance-induced abnormalities in the hippocampus of obese/T2D patients, such as inflammatory stress, oxidative stress, and mitochondrial stress, increased generation of advanced glycated end products and BBB dysfunction, as well as their association with dementia/Alzheimer's disease, are addressed. Finally, we discuss how these abnormalities are accompained by the reduction in the expression and translocation of the high capacity insulin-sensitive glucose transporter GLUT4 in hippocampal neurons, which leads to neurocytoglycopenia and eventually to cognitive dysfunction. This knowledge should further encourage investigations into the beneficial effects of promising therapeutic approaches which could improve central insulin sensitivity and GLUT4 expression, to fight diabetes-related cognitive dysfunctions.

Intermittent training followed by detraining provides the preservation of hepatic tissue and body composition of eutrophic rats in relation to obese rats after the detraining period / El entrenamiento intermitente seguido de desacondicionamiento facilita la preservación del tejido hepático y la composición corporal de las ratas eutróficas en relación a las ratas obesas después del período de desacondicionamiento

The aim of the study was to evaluate the effects of intermittent training followed by detraining on liver tissue and body composition of rats subjected to a normolipidic or hyperlipidic diet. Sixty Wistar rats were divided into the groups Sedentary Control (SC), Exercised Control (EC), Sedentary Control euthanized at six months of age (SC(6)), Detrained Control (DC), Sedentary Obese (SO), Exercised Obese (EO), Sedentary Obese euthanized at six months of age (SO(6)) and Detrained Obese (DO), which performed intermittent training for eight weeks. After, the groups SC(6), DC, SO(6) and DO performed a detraining protocol for eight weeks. The animals were euthanized, with measurements of body mass and length taken, and retrieval of Epididymal Adipose Tissue (EAT) for body composition variables and the liver for karyometric and stereological analysis. Significant differences were found in the liver mass values of the EC relative to the DO and in the SO(6) liver in relation to all groups, with a greater gain in body mass of the SO(6) in comparison to the EC; in the EAT total, EAT percentage and BM of SO(6) and DO in relation to the EC and the DC and in the karyometric variables of the EC and the DC in relation to EO and DO, with no differences in the stereology and on the Lee index between all groups. Intermittent training showed better effects on the DC liver tissue compared to EO and DO, and on the EC and DC body composition compared to SO(6) and DO.

El objetivo del estudio fue evaluar los efectos del entrenamiento intermitente seguido de desentrenamiento en el tejido hepático y la composición corporal de ratas sometidas a una dieta normolipídica e hiperlipídica. Sesenta ratas Wistar se dividieron en los siguientes grupos: Control Sedentario (CS), Control Entrenado (CE), Control Sedentario sacrificado a los seis meses de edad (SC (6)), Control Desentrenado (CD), Obeso Sedentario (OS), Obeso Entrenado (OE), Obesidad Sedentaria sacrificados a los seis meses de edad (OS) (6)) y Obesidad Desentrenada (DOD), que realizó un entrenamiento intermitente durante ocho semanas. Posteriormente, los grupos CS (6), CD, OS (6) y DO realizaron un protocolo de desentrenamiento durante ocho semanas. Los animales fueron sacrificados, con mediciones de masa corporal y longitud, y la recuperación de tejido adiposo epididimal (EAT) para las variables de composición corporal y el hígado para el análisis estereológico y cariométrico. Se encontraron diferencias significativas en los valores de la masa hepática de CE en relación con DO y en el hígado SO (6) en relación con todos los grupos, con un mayor aumento en la masa corporal del SO (6) en comparación con la CE; en el total de EAT, porcentaje de EAT y BM de SO (6) y OD en relación con CE y CD y en las variables cariométricas de CE y CD en relación con OE y OD, sin diferencias en la estereología y en el índice de Lee entre todos los grupos. En el entrenamiento intermitente se observaron mejores efectos en el tejido hepático de CD en comparación con OE y OD, y en la composición corporal de CE y CD en comparación con OS (6) y OD.

Can the intermittent training generate alterations on the liver tissue of rats submitted to a hyperlipidic diet? / ¿El entrenamiento intermitente puede generar alteraciones sobre el tejido hepático de ratas sometidas a una dieta alta en grasa?

Studies indicate that increasing physical activity and decreasing levels of fat in the liver help to decrease the risk of morbidity from liver conditions. This study aimed to evaluate the effects of an eight week intermittent training program on the liver tissue of rats subjected to a hyperlipidic diet. The study consisted of 30 male Wistar rats, divided into the following groups: Sedentary Control (SC) Exercise Control (EC) (fed on standard feed and water) Sedentary Obese (SO) and Exercise Obese (EO) (fed on bacon, ham, sausage, biscuits, soda and standard feed), which performed intermittent training through electrically stimulated jumps, with three sets of 12 repetitions, three times per week for eight weeks. At the end of the training period, the animals were euthanized, and their livers removed for histological processing and hematoxylin and eosin staining (HE). Soon afterwards, caryometric analysis of the hepatocyte nuclei was performed. From the presented results it can be seen that the hepatocyte nuclei of the obese animals were smaller in relation to those of the control animals, therefore, exercise combined with an appropriate diet proved to be efficient in not causing alterations in the hepatocyte nuclei, conserving normal cell function and reducing the chances of the appearance of tissue damage. Furthermore, exercise in isolation cannot be considered a protective factor against the alteration of the liver cells.

Estudios indican que el aumento de la actividad física y la disminución de los niveles de grasa en el hígado ayudan a reducir el riesgo de morbilidad por enfermedades hepáticas. El objetivo fue evaluar el efecto de un programa de entrenamiento intermitente de ocho semanas en el tejido hepático de ratas con dieta alta en grasa. Treinta ratas Wistar machos fueron divididas en grupos Control Sedentario (SC), Control Ejercicio (CE) (con fuente de alimentación que consiste en la ración estándar y agua), Obeso Sedentario (OS) y Obeso Ejercicio (OE) (con alimentación compuesta por tocino, mortadela, salchichas, galletas, refrescos y ración estándar), sometidas a un entrenamiento intermitente a través de saltos mediante estimulación eléctrica con tres series de 12 repeticiones, tres veces por semana durante ocho semanas. Al final del período de entrenamiento, los animales fueron sacrificados; se extrajeron sus hígados para el procesamiento histológico y tinción con hematoxilina y eosina (HE). Luego se realizó el análisis cariométrico de los núcleos de los hepatocitos. Se observó que los núcleos de los hepatocitos fueron menores en los animales obesos en comparación con los núcleos de hepatocitos de los animales de control, pues el ejercicio combinado con una dieta adecuada se mostró eficiente para que causar alteraciones en los núcleos de hepatocitos, y esa combinación puede retener la función normal de las células y disminuir las posibilidades de la aparición de daños en los tejidos. Además, el ejercicio aislado no puede ser considerado como un factor de protección contra la alteración las células del hígado.

Respostas lactacidêmicas de ratos ao treinamento intermitente de alta intensidade / Blood lactate responses to high-intensity intermittent training in rats

Durante contrações musculares de alta intensidade intervaladas por curtos períodos de tempo há importante participação do metabolismo glicolítico e, consequentemente, aumento das concentrações de lactato sanguíneo. O objetivo do estudo foi avaliar as respostas lactacidêmicas agudas e crônicas de ratos Wistar submetidos a um treinamento intermitente de alta intensidade (salto tipo jump squat) de três sessões semanais, a cada 24h, três séries de 12 repetições com intervalos de 60s entre cada uma. Houve aumento das concentrações de lactato sanguíneo durante a sessão aguda do treinamento (lactacidemia basal vs. lactacidemia após último esforço, P < 0,001). Contrariamente, após seis semanas de treinamento, ocorreu redução de 49% na resposta lactacidêmica ao exercício em relação à primeira sessão, P = 0,0002. O exercício intermitente de alta intensidade intervalado favorece a participação do sistema glicolítico; no entanto, o treinamento intermitente de alta intensidade promove redução das respostas lactacidêmicas, sugerindo melhora da capacidade de ressíntese de fosfocreatina e da biogênese mitocondrial.

During high-intensity intermittent muscle contractions for short periods of time there is an important involvement of glycolytic metabolism and consequent increased blood lactate concentrations. This study aimed to evaluate the blood lactate responses in Wistar rats submitted to high-intensity intermittent training (jump squat) protocol during 6 weeks, 3 sessions, 12 x/session, 60s of interval between sessions. There was significant increase of blood lactate concentrations during the acute bout of high-intensity intermittent exercise (basal blood lactate vs blood lactate after last effort, P<0.001); however, after six weeks of training, there was significant reduction (49%) in blood lactate response to the exercise in comparison to the first session, P=0.0002. The high-intensity intermittent exercise performed at intervals of 60 seconds stimulated the glycolytic system; nevertheless, the training promoted reduction in blood lactate responses to high-intensity intermittent protocol, suggesting hence improvement in phosphocreatine recovery capacity and in mitochondrial biogenesis.

[Resistive training reduces inflammation in skeletal muscle and improves the peripheral insulin sensitivity in obese rats induced by hyperlipidic diet]. / Treinamento resistido reduz inflamação em músculo esquelético e melhora a sensibilidade à insulina periférica em ratos obesos induzidos por dieta hiperlipídica.

OBJECTIVE: To determine if resistive exercise protocol can modulate Tnf-α, SOCS3 and glucose transporter GLUT4 genes expression in skeletal muscle, and peripheral insulin sensitivity in obese rats induced by hyperlipidic diet. MATERIALS AND METHODS: Wistar obese rats induced by hyperlipidic diet were subjected a resistive exercise protocol as jump squat. Insulin sensitivity and mRNA content of Tnf-α, SOCS3 and GLUT4 were assayed and compared among the groups: obese sedentary (OS) and exercised (OE), control sedentary (CS) and exercised (CE). RESULTS: The mRNA content of Tnf-α and SOCS3 has increased in skeletal muscle from OS and has decreased in OE group. The protein and GLUT4 mRNA contents were correlated but they did not change among the groups. Peripheral insulin sensitivity has increased in the OE compared to OS group. CONCLUSION: The resistive exercise reverses the peripheral insulin resistance and the inflammatory state in skeletal muscle from diet-induced obese rats.

Treinamento resistido reduz inflamação em músculo esquelético e melhora a sensibilidade à insulina periférica em ratos obesos induzidos por dieta hiperlipídica / Resistive training reduces inflammation in skeletal muscle and improves the peripheral insulin sensitivity in obese rats induced by hyperlipidic diet

OBJETIVO: Investigar em ratos obesos o efeito da prática de exercício resistido sobre a sensibilidade à insulina e sobre a expressão de citocinas pró-inflamatórias e de transportador de glicose em músculo solear. MATERIAIS E MÉTODOS: Ratos Wistar alimentados com dieta hiperlipídica (grupos obesos) foram submetidos ao protocolo de exercício tipo jump squat. A sensibilidade à insulina e a expressão gênica de Tnf-α, SOCS3 e GLUT4 foram comparadas entre os grupos obesos sedentários (OS) e exercitados (OE) e controles sedentários (CS) e exercitados (CE). RESULTADOS: A sensibilidade à insulina estava reduzida no grupo OS e elevada no OE. Os conteúdos de RNAm de Tnf-α e de SOCS3 estavam aumentados no músculo esquelético do grupo OS e reduzidos no OE. O conteúdo proteico e de RNAm de GLUT4 não diferiu entre os grupos. CONCLUSÃO: O exercício resistido reverte o quadro de resistência à insulina periférica e de inflamação no músculo esquelético de obesos induzidos por dieta.

OBJECTIVE: To determine if resistive exercise protocol can modulate Tnf-α, SOCS3 and glucose transporter GLUT4 genes expression in skeletal muscle, and peripheral insulin sensitivity in obese rats induced by hyperlipidic diet. MATERIALS AND METHODS: Wistar obese rats induced by hyperlipidic diet were subjected a resistive exercise protocol as jump squat. Insulin sensitivity and mRNA content of Tnf-α, SOCS3 and GLUT4 were assayed and compared among the groups: obese sedentary (OS) and exercised (OE), control sedentary (CS) and exercised (CE). RESULTS: The mRNA content of Tnf-α and SOCS3 has increased in skeletal muscle from OS and has decreased in OE group. The protein and GLUT4 mRNA contents were correlated but they did not change among the groups. Peripheral insulin sensitivity has increased in the OE compared to OS group. CONCLUSION: The resistive exercise reverses the peripheral insulin resistance and the inflammatory state in skeletal muscle from diet-induced obese rats.