Melatonin has a number of beneficial metabolic actions and reduced levels of melatonin may contribute to type 2 diabetes. The present study investigated the metabolic pathways involved in the effects of melatonin on mitochondrial function and insulin resistance in rat skeletal muscle. The effect of melatonin was tested both in vitro in isolated rats skeletal muscle cells and in vivo using pinealectomized rats (PNX). Insulin resistance was induced in vitro by treating primary rat skeletal muscle cells with palmitic acid for 24 hr. Insulin-stimulated glucose uptake was reduced by palmitic acid followed by decreased phosphorylation of AKT which was prevented my melatonin. Palmitic acid reduced mitochondrial respiration, genes involved in mitochondrial biogenesis and the levels of tricarboxylic acid cycle intermediates whereas melatonin counteracted all these parameters in insulin-resistant cells. Melatonin treatment increases CAMKII and p-CREB but had no effect on p-AMPK. Silencing of CREB protein by siRNA reduced mitochondrial respiration mimicking the effect of palmitic acid and prevented melatonin-induced increase in p-AKT in palmitic acid-treated cells. PNX rats exhibited mild glucose intolerance, decreased energy expenditure and decreased p-AKT, mitochondrial respiration, and p-CREB and PGC-1 alpha levels in skeletal muscle which were restored by melatonin treatment in PNX rats. In summary, we showed that melatonin could prevent mitochondrial dysfunction and insulin resistance via activation of CREB-PGC-1 alpha pathway. Thus, the present work shows that melatonin play an important role in skeletal muscle mitochondrial function which could explain some of the beneficial effects of melatonin in insulin resistance states.

ABSTRACT:Objective: To analyze the occurrence of sleep-related disorders among adults from Presidente Prudente, Brazil, as well as to identify associations with behavioral, socio-demographic and nutritional status variables. Methods: After random selection of the sample, interviews were performed with 743 adults of both genders, living in Presidente Prudente, Brazil. Sleep-related disorders, demographic variables (sex, age, ethnicity and schooling), behavioral variables (leisure physical activity, alcohol consumption, and smoking) and nutritional status were analyzed by questionnaires. Results: The prevalence of sleep-related disorders was 46.7%, with 95% confidence interval (95%CI) 43.1 -50.2. In the multivariate analysis, female sex, with odds ratio (OR) 1.74 (95%CI 1.26 -2.40), schooling (OR = 0.49; 95%CI 0.28 -0.82), overweight (OR = 1.99; 95%CI 1.39 -2.85) and obesity (OR = 2.90; 95%CI 1.94 -4.35) were associated with sleep-related disorders. Conclusion: There is high occurrence of sleep-related disorders in this sample, which was associated with female sex, lower schooling, overweight and obesity.

Mitochondria play a critical role in several cellular processes and cellular homeostasis. Mitochondrion dysfunction has been correlated with numerous metabolic diseases such as obesity and type 2 diabetes. MicroRNAs are non-coding RNAs that have emerged as key regulators of cell metabolism. The microRNAs act as central regulators of metabolic gene networks by leading to the degradation of their target messenger RNA or repression of protein translation. In addition, vesicular and non-vesicular circulating miRNAs exhibit a potential role as mediators of the cross-talk between the skeletal muscle and other tissues/organs. In this review, we will focus on the emerging knowledge of miRNAs controlling mitochondrial function and insulin signaling in skeletal muscle cells. J. Cell. Physiol. 232: 958-966, 2017. © 2016 Wiley Periodicals, Inc.

Diabetes mellitus is a chronic disease that has been associated with memory loss, neurological disorders, and Alzheimer's disease. Some studies show the importance of physical exercise to prevent and minimize various neurological disorders. It is believed that the positive effects of exercise on brain functions are mediated by brain insulin and insulin-like growth factor-1 (IGF-1) signaling. In this study, we investigate the role of swimming exercise training on hippocampus proteins related to insulin/IGF-1 signaling pathway in Type 1 diabetic rats and its effects on spatial memory. Wistar rats were divided into four groups namely sedentary control, trained control, sedentary diabetic (SD), and trained diabetic (TD). Diabetes was induced by Alloxan (ALX) (32 mg/kg b.w.). The training program consisted in swimming 5 days/week, 1 h/day, per 6 weeks, supporting an overload corresponding to 90% of the anaerobic threshold. We employed ALX-induced diabetic rats to explore learning and memory abilities using Morris water maze test. At the end of the training period, the rats were sacrificed 48 h after their last exercise bout when blood samples were collected for serum glucose, insulin, and IGF-1 determinations. Hippocampus was extracted to determinate protein expression (IR, IGF-1R, and APP) and phosphorylation (AKT-1, AKT-2, Tau, and β-amyloide proteins) by Western Blot analysis. All dependent variables were analyzed by two-way analysis of variance with significance level of 5%. Diabetes resulted in hyperglycemia and hypoinsulinemia in both SD and TD groups (P < 0.05); however, in the training-induced group, there was a reduction in blood glucose in TD. The average frequency in finding the platform decreased in SD rats; however, exercise training improved this parameter in TD rats. Aerobic exercise decreased Tau phosphorylation and APP expression, and increased some proteins related to insulin/IGF-1 pathway in hippocampus of diabetic rats. Thus, these molecular adaptations from exercise training might contribute to improved spatial learning and memory in diabetic organisms.

Obesity is a public health issue that affects more than 600 million adults worldwide. The disease is characterized by fat accumulation, mainly in the abdominal area. The human body is mainly composed of two types of adipose tissue: white adipose tissue (WAT) and brown adipose tissue (BAT); however, the browning process generates a different type of brown fat-like adipocyte in WAT, which similar to BAT has thermogenic capacity by activating UCP-1. The hypothalamic arcuate nucleus plays an important role in WAT browning via POMC neurons, which are influenced by synergistic insulin and leptin signaling. On the other hand, stimulation of AgRP neurons suppresses WAT browning. The hypothalamic inflammatory process that occurs in obesity impairs insulin and leptin signaling in this tissue and, consequently, can decrease WAT browning. In addition, practicing physical exercise may be a great strategy for triggering the browning process since it reduces hypothalamic inflammation and increases POMC neurons gene expression. Moreover, physical exercise stimulates irisin gene expression, which has an important impact on thermogenesis, which in turn culminates in increased gene expression of proteins such as UCP-1 and Cidea, which are related to WAT browning. Furthermore, thermogenetic activation of WAT leads to increased energy expenditure, favoring obesity treatment. Therefore, this mini-review aimed to highlight the most recent studies that link the control of hypothalamic activity with the browning metabolism of adipose tissue in response to physical exercise.

BackgroundThe objective of this study was to determine the effects of creatine supplementation on liver biomarkers of oxidative stress in exercise-trained rats.MethodsForty 90-day-old adult male Wistar rats were assigned to four groups for the eight-week experiment. Control group (C) rats received a balanced control diet; creatine control group (CCr) rats received a balanced diet supplemented with 2% creatine; trained group (T) rats received a balanced diet and intense exercise training equivalent to the maximal lactate steady state phase; and supplemented-trained (TCr) rats were given a balanced diet supplemented with 2% creatine and subjected to intense exercise training equivalent to the maximal lactate steady state phase. At the end of the experimental period, concentrations of creatine, hydrogen peroxide (H2O2) and thiobarbituric acid reactive substances (TBARS) were measured as well as the enzyme activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-GPx) and catalase (CAT). Liver tissue levels of reduced glutathione (GSH), oxidized glutathione (GSSG) and the GSH/GSSG ratio were also determined.ResultsHepatic creatine levels were highest in the CCr and TCr groups with increased concentration of H2O2 observed in the T and TCr animal groups. SOD activity was decreased in the TCr group. GSH-GPx activity was increased in the T and TCr groups while CAT was elevated in the CCr and TCr groups. GSH, GGS and the GSH/GSSG ratio did not differ between all animal subsets.ConclusionsOur results demonstrate that creatine supplementation acts in an additive manner to physical training to raise antioxidant enzymes in rat liver. However, because markers of liver oxidative stress were unchanged, this finding may also indicate that training-induced oxidative stress cannot be ameliorated by creatine supplementation.

Newborn rats (6 days old) received alloxan intraperitoneally (A= 250 mg/kg b.w). Rats injected with vehicle (citrate buffer) were used as controls (C). After weaning, half of the animals were submitted to 1 hour/day, 5 days/week swimming and with supporting overload of 5% b.w. At 28 days, no signifi cant differences were found among the groups in fasting glycemia and insulinemia. At 60 days, the fasting glycemia (30 min after oral glucose administration) was higher in alloxan than in controls groups and lower in the alloxan group submitted to training than in the correspondent sedentary group. The glucose tolerance of the alloxan rats was reduced in comparison to controls, both at 28 and 60 days, since the area under the blood glucose curve during the OGTT was higher in the alloxan than in the control. No difference was found among the groups both at 28 and 60 days in the HOMA index. However, a slight reduction was observed in the values of the trained groups suggesting slightly increased insulin sensitivity in the animals. These results suggest that this diabetes mellitus animal model presents interesting characteristics for the study of the role of the physical exercise in diabetes outcome.

Abstract-The purpose of this study was to evaluate the effect of creatine supplementation in the diet on indicators of glucose metabolism in skeletal muscle of exercised rats. Forty Wistar adult rats were distributed into four groups for eight weeks: 1) Control: sedentary rats that received balanced diet; 2) Creatine control: sedentary rats that received supplementation of 2% creatine in the balanced diet; 3) Trained: rats that ran on a treadmill at the Maximal Lactate Steady State and received balanced diet; and 4) Supplemented-trained: rats that ran on a treadmill at the Maximal Lactate Steady State and received creatine supplementation (2%) in the balanced diet. The hydric intake increased and the body weight gain decreased in the supplemented-trained group. In the soleus muscle, the glucose oxidation increased in both supplemented groups. The production of lactate and glycemia during glucose tolerance test decreased in the supplemented-trained group. Creatine supplementation in conjunction with exercise training improved muscular glycidic metabolism of rats.Keywords: somatic index, glucose tolerance, physical activity Resumo-"Influência da suplementação com creatina em indicadores de metabolismo da glucose no músculo esquelético de ratos exercitados." O objetivo deste estudo foi avaliar o efeito da suplementação de creatina na dieta sobre indicadores do metabolismo glicídico musculoesquelético de ratos exercitados. Quarenta ratos Wistar adultos foram divididos em quatro grupos por oito semanas: Controle: receberam dieta balanceada, mantidos sedentários; Controle Creatina: receberam suplementação de creatina (2%) na dieta balanceada, mantidos sedentários; Treinado: correram em esteira na intensidade da máxima fase estável de lactato e receberam a dieta balanceada e grupo Treinado Suplementado: correram em esteira na intensidade da máxima fase estável de lactato e receberam suplementação de creatina (2%) na dieta balanceada. A ingestão hídrica aumentou e o ganho de massa corporal reduziu no grupo treinado e suplementado. No músculo sóleo, a oxidação de glicose aumentou em ambos os grupos suplementados. A produção de lactato e a glicemia durante teste de tolerância à glicose diminuíram no grupo treinado e suplementado. A suplementação com creatina em conjunto com treinamento físico melhorou metabolismo de glicídico muscular dos ratos.Palavras-chaves: índice somático, tolerância à glicose, atividade físicaResumen-"Influencia de la suplementación con creatina sobre indicadores del metabolismo de la glucosa en el músculo esquelético de ratas ejercitadas." El objetivo de este estudio fue evaluar el efecto de la suplementación con creatina en la dieta sobre indicadores del metabolismo de glucosa en el músculo esquelético en ratones ejercitados. Cuarenta ratas macho adultas Wistar se dividieron en cuatro grupos de ocho semanas: Control: recibieron dieta equilibrada, mantenido sedentaria; Control Complementado: La suplementación con creatina recibido (2%) en la dieta equilibrada, sedentaria mantenido; Trained: corrien...