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The purpose of this study was to characterize aerobic, anaerobic, handgrip strength, and body fat content (BF) characteristics in paralympic rowers (ROW) in order to determine motor disabled rowers' fitness level and if specific motor disabilities could impair performance in this specific population. Upper body anaerobic threshold (LacT), peak (PK-AnP), mean (M-AnP), and lower (L-AnP) anaerobic power, peak anaerobic power to weight ratio (RelPk-AnP) and fatigue index (FI) were measured by the Wingate test (WinT). Handgrip strength was also measured and skinfold sum was used to estimate BF and were compared with a reference group of recreational disabled athletes (CON). LacT was significantly higher (p < 0.01) in ROW compared with CON. RelPk-AnP and BF were significantly different (p < 0.05) in ROW compared with CON as well. All other measured parameters did not significantly differ between ROW and CON. In most of cases, rowers have shown a relative low performance level, induced probably by specific disabilities. [ABSTRACT FROM AUTHOR]

Objective: The objective of the present study was to analyze the effects of 10 weeks of resistance training (RT) and subsequent 4 weeks of detraining on physical function, body composition, and biochemical markers in aging adults., Methods: The study sample was selected by convenience and consisted of 12 women with a mean age of 58 ± 7 years. Physical function [Latin-American Group of Development for Maturity (GDLAM) general index], body composition, total and fractional cholesterol, triglycerides, and glycemia were assessed before and after RT (10 weeks) and detraining (4 weeks)., Results: After 10 weeks of RT, there were improvements in fat-free mass (39.1 ± 4.2 vs. 39.9 ± 4.4 kg; p < 0.05 and d = 0.2), fat mass (39.9 ± 6.3% vs. 38.7 ± 6.4%; p < 0.05 and d = -0.2), conicity index (1.47 ± 0.07 vs. 1.43 ± 0.06; p = 0.001 and d = -0.6), and physical function (GDLAM index [27.2 ± 5.5 vs. 25.0 ± 4.7; p = 0.001 and d = -0.4]). Significant improvements were also found in total cholesterol (271.8 ± 75.7 vs. 217.2 ± 52.2 mg/dL; p < 0.01 and d = -0.8), LDL-cholesterol (196.5 ± 61.6 vs. 159.3 ± 38.5 mg/dL; p < 0.01 and d = -0.7), HDL-cholesterol (53.1 ± 7.3 vs. 64.3 ± 23.7 mg/dL; p < 0.05 and d = 0.7), and triglycerides (165.8 ± 32.6 vs. 139.9 ± 46.6 mg/dL; p = 0.001 and d = -0.6). After the detraining period, all benefits in physical function were successfully maintained., Conclusion: RT provided benefits in physical function, body composition, and biochemical markers in aging adults. However, 4-week detraining impaired body composition and biochemical markers in the investigated sample., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aim Investigate whether inheritance of improved skeletal muscle mitochondrial function and its association with glycemic control are multigenerational benefits of exercise., Main Methods: Male Swiss mice were subjected to 8 weeks of endurance training and mated with untrained females., Key Findings: Trained fathers displayed typical endurance training-induced adaptations. Remarkably, offspring from trained fathers also exhibited higher endurance performance, mitochondrial oxygen consumption, glucose tolerance and insulin sensitivity. However, PGC-1α expression was not increased in the offspring. In the offspring, the expression of the co-repressor NCoR1 was reduced, increasing activation of PGC-1α target genes. These effects correlated with higher DNA methylation at the NCoR1 promoter in both, the sperm of trained fathers and in the skeletal muscle of their offspring., Significance: Higher skeletal muscle mitochondrial function is inherited by epigenetic de-activation of a key PGC-1α co-repressor., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Bile acid tauroursodeoxycholic (TUDCA), formed from the association of ursodeoxycholic acid (UDCA) with taurine, has already been shown to increase mitochondrial biogenesis and cell survival, in addition to reduce reticulum stress markers in different cell types. However, its mechanism of action upon insulin secretion control in obesity is still unknown. In this sense, we seek to clarify whether taurine, associated with bile acid, could improve the function of the pancreatic β-cells exposed to fatty acids through the regulation of mitochondrial metabolism. To test this idea, insulin-producing cells (INS1-E) were exposed to a fatty acid mix containing 500 μM of each palmitate and oleate for 48 hours treated or not with 300 μM of TUDCA. After that, glucose-stimulated insulin secretion and markers of mitochondrial metabolism were evaluated. Our results showed that the fatty acid mix was efficient in inducing hyperfunction of INS1-E cells as observed by the increase in insulin secretion, protein expression of citrate synthase, and mitochondrial density, without altering cell viability. The treatment with TUDCA normalized insulin secretion, reducing the protein expression of citrate synthase, mitochondrial mass, and the mitochondrial membrane potential. This effect was associated with a decrease in the generation of mitochondrial superoxide and c-Jun N-terminal kinase (JNK) protein content. The findings are also consistent with the hypothesis that TUDCA normalizes insulin secretion by improving mitochondrial metabolism and redox balance. Thus, it highlights likely mechanisms of the action of this bile acid on the glycemic homeostasis reestablishment in obesity., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Background/aims: Epigenetic regulation is considered the main molecular mechanism underlying the developmental origin of health and disease's (DOHAD) hypothesis. Previous studies that have investigated the role of paternal exercise on the metabolic health of the offspring did not control for the amount and intensity of the training or possible effects of adaptation to exercise and produced conflicting results regarding the benefits of parental exercise to the next generation. We employed a precisely regulated exercise regimen to study the transgenerational inheritance of improved metabolic health., Methods: We subjected male mice to a well-controlled exercise -training program to investigate the effects of paternal exercise on glucose tolerance and insulin sensitivity in their adult progeny. To investigate the molecular mechanisms of epigenetic inheritance, we determined chromatin markers in the skeletal muscle of the offspring and the paternal sperm., Results: Offspring of trained male mice exhibited improved glucose homeostasis and insulin sensitivity. Paternal exercise modulated the DNA methylation profile of PI3Kca and the imprinted H19/Igf2 locus at specific differentially methylated regions (DMRs) in the skeletal muscle of the offspring, which affected their gene expression. Remarkably, a similar DNA methylation profile at the PI3Kca, H19, and Igf2 genes was present in the progenitor sperm indicating that exercise-induced epigenetic changes that occurred during germ cell development contributed to transgenerational transmission., Conclusion: Paternal exercise might be considered as a strategy that could promote metabolic health in the offspring as the benefits can be inherited transgenerationally.

Background and Aims: Malnutrition in the early stages of life may lead to changes in the glycemic metabolism during adulthood, such as pancreatic beta cells dysfunction and failure. Therefore, this study aimed to evaluate the effects of an in vitro amino acid restriction model on the function and viability of pancreatic beta cells., Methods: Insulin-producing cells (INS-1E) were maintained in control or amino acid restricted culture medium containing 1 × or 0.25 × of amino acids, respectively, for 48 h., Results: Amino acid restricted group showed lower insulin secretion and insulin gene expression, reduced mitochondrial oxygen consumption rate and reactive oxygen species production. Besides, amino acid restricted group also showed higher levels of endoplasmic reticulum stress and apoptosis markers and enhanced Akt phosphorylation. However, even with higher levels of apoptosis markers, amino acid restricted group did not show higher levels of cell death unless the PI3K/Akt pathway was inhibited., Conclusion: Amino acid restricted beta cell viability seems to be dependent on the PI3K/Akt pathway., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Malnutrition programs metabolism, favor dysfunction of β cells. We aimed to establish an in vitro protocol of malnutrition, assessing the effect of amino acid restriction upon the β cells. Insulin-producing cells INS-1E and pancreatic islets were maintained in RPMI 1640 medium containing 1× (Ctl) or 0.25× (AaR) of amino acids. We evaluated several markers of β-cell function and viability. AaR Insulin secretion was reduced, whereas cell viability was unaltered. Calcium oscillations in response to glucose increased in AaR. AaR showed lower Ins1 RNAm, snap 25, and PKC (protein kinase C) protein content, whereas phospho-eIF2α was increased. AaR cells exposed to nutrient or chemical challenges displayed higher apoptosis rates. We showed that amino acid restriction programmed β cell and induced functional changes. This model might be useful for the study of molecular mechanisms involved with β-cell programming helping to establish novel therapeutic targets to prevent harmful outcomes of malnutrition., (© 2019 Wiley Periodicals, Inc.)

Nutrient malnutrition, during the early stages of development, may facilitate the onset of metabolic diseases later in life. However, the consequences of nutritional insults, such as a high-fat diet (HFD) after protein restriction, are still controversial. We assessed overall glucose homeostasis and molecular markers of mitochondrial function in the gastrocnemius muscle of protein-restricted mice fed an HFD until early adulthood. Male C57BL/6 mice were fed a control (14% protein-control diet) or a protein-restricted (6% protein-restricted diet) diet for 6 weeks. Afterward, mice received an HFD or not for 8 weeks (mice fed a control diet and HFD [CH] and mice fed a protein-restricted diet and HFD [RH]). RH mice showed lower weight gain and fat accumulation and did not show an increase in fasting plasma glucose and insulin levels compared with CH mice. RH mice showed higher energy expenditure, increased citrate synthase, peroxisome-proliferator-activated receptor gamma coactivator 1-alpha protein content, and higher levels of malate and α-ketoglutarate compared with CH mice. Moreover, RH mice showed increased AMPc-dependent kinase and acetyl coenzyme-A (CoA) carboxylase phosphorylation, lower intramuscular triacylglycerol content, and similar malonyl-CoA levels. In conclusion, protein undernourishment after weaning does not potentiate fat accumulation and insulin resistance in adult young mice fed an HFD. This outcome seems to be associated with increased skeletal muscle mitochondrial oxidative capacity and reduced lipids accumulation., (© 2018 Wiley Periodicals, Inc.)

The practice of physical exercise is highly indicated to prevent cardiovascular diseases and is directly related to the improvement of endothelial function and the regulation of arterial blood pressure. The objective of this study was to analyze the effect of physical exercise in vascular remodeling after FeCl 3 chemically induced arterial injury on atherosclerotic mice. To analyze the effect of exercises on thrombus formation, LDL receptor-deficient mice were fed for 6 weeks with a high-fat diet and performed or not physical exercises for 2 weeks before the arterial injury. To verify endothelium recovery the animals were exercised or not 2 weeks before the injury, and 3 weeks after it, when the vessels were analyzed. In this work, we observed that physical exercises done only before arterial injury reduced thrombosis time, protected the endothelial layer, promoted the recruitment of CD34 positive progenitor cells, increased the level of eNOS and gelatinases activities and decreased the number of inflammatory cells in the vessel, but do not avoid the growth of neointima. Otherwise exercises done before and continued after injury, increased gelatinase activities, reduced lipid deposition in the aortic arch and prevented neointima formation. Thus, we could conclude that physical exercises are done before and continued after endothelial injury stimulate endothelial recovery by promoting endothelial cell growth, matrix remodeling and decreasing inflammation in the vessel wall., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Prolonged exercise has positive metabolic effects in obese or diabetic individuals. These effects are usually ascribed to improvements in insulin sensitivity. We evaluated whether exercise also generates circulating signals that protect human and rodent β cells against endoplasmic reticulum (ER) stress and apoptosis. For this purpose, we obtained serum from humans or mice before and after an 8 wk training period. Exposure of human islets or mouse or rat β cells to human or rodent sera, respectively, obtained from trained individuals reduced cytokine (IL-1β+IFN-γ)- or chemical ER stressor-induced β-cell ER stress and apoptosis, at least in part via activation of the transcription factor STAT3. These findings indicate that exercise training improves human and rodent β-cell survival under diabetogenic conditions and support lifestyle interventions as a protective approach for both type 1 and 2 diabetes.-Paula, F. M. M., Leite, N. C., Borck, P. C., Freitas-Dias, R., Cnop, M., Chacon-Mikahil, M. P. T., Cavaglieri, C. R., Marchetti, P., Boschero, A. C., Zoppi, C. C., Eizirik, D. L. Exercise training protects human and rodent β cells against endoplasmic reticulum stress and apoptosis.

In the present study, we investigated the relationship between early life protein malnutrition-induced redox imbalance, and reduced glucose-stimulated insulin secretion. After weaning, male Wistar rats were submitted to a normal-protein-diet (17%-protein, NP) or to a low-protein-diet (6%-protein, LP) for 60 days. Pancreatic islets were isolated and hydrogen peroxide (H 2 O 2 ), oxidized (GSSG) and reduced (GSH) glutathione content, CuZn-superoxide dismutase (SOD1), glutathione peroxidase (GPx1) and catalase (CAT) gene expression, as well as enzymatic antioxidant activities were quantified. Islets that were pre-incubated with H 2 O 2 and/or N-acetylcysteine, were subsequently incubated with glucose for insulin secretion measurement. Protein malnutrition increased CAT mRNA content by 100%. LP group SOD1 and CAT activities were 50% increased and reduced, respectively. H 2 O 2 production was more than 50% increased whereas GSH/GSSG ratio was near 60% lower in LP group. Insulin secretion was, in most conditions, approximately 50% lower in LP rat islets. When islets were pre-incubated with H 2 O 2 (100 μM), and incubated with glucose (33 mM), LP rats showed significant decrease of insulin secretion. This effect was attenuated when LP islets were exposed to N-acetylcysteine., (© 2017 Wiley Periodicals, Inc.)

Taurine (Tau) restores β-cell function in obesity; however, its action is lost in malnourished obese rodents. Here, we investigated the mechanisms involved in the lack of effects of Tau in this model. C57BL/6 mice were fed a control diet (CD) (14% protein) or a protein-restricted diet (RD) (6% protein) for 6 wk. Afterward, mice received a high-fat diet (HFD) for 8 wk [CD + HFD (CH) and RD + HFD (RH)] with or without 5% Tau supplementation after weaning on their drinking water [CH + Tau (CHT) and RH + Tau (RHT)]. The HFD increased insulin secretion through mitochondrial metabolism in CH and RH. Tau prevented all those alterations in CHT only. The expression of the taurine transporter (Tau-T), as well as Tau content in pancreatic islets, was increased in CH but had no effect on RH. Protein malnutrition programs β cells and impairs Tau-induced restoration of mitochondrial metabolism and biogenesis. This may be associated with modulation of the expression of Tau-T in pancreatic islets, which may be responsible for the absence of effect of Tau in protein-malnourished obese mice.-Branco, R. C. S., Camargo, R. L., Batista, T. M., Vettorazzi, J. F., Borck, P. C., dos Santos-Silva, J. C. R., Boschero, A. C., Zoppi, C. C., Carneiro, E. M. Protein malnutrition blunts the increment of taurine transporter expression by a high-fat diet and impairs taurine reestablishment of insulin secretion., (© FASEB.)

Pancreatic beta cell (β) dysfunction is an outcome of malnutrition. We assessed the role of the amplifying pathway (AMP PATH) in β cells in malnourished obese mice. C57Bl-6 mice were fed a control (C) or a low-protein diet (R). The groups were then fed a high-fat diet (CH and RH). AMP PATH contribution to insulin secretion was assessed upon incubating islets with diazoxide and KCl. CH and RH displayed increased glucose intolerance, insulin resistance and glucose-stimulated insulin secretion. Only RH showed a higher contribution of the AMP PATH. The mitochondrial membrane potential of RH was decreased, and ATP flux was unaltered. In RH islets, glutamate dehydrogenase (GDH) protein content and activity increased, and the AMP PATH contribution was reestablished when GDH was blunted. Thus, protein malnutrition induces mitochondrial dysfunction in β cells, leading to an increased contribution of the AMP PATH to insulin secretion through the enhancement of GDH content and activity.

Type 1 diabetes (T1D) is provoked by an autoimmune assault against pancreatic β cells. Exercise training enhances β-cell mass in T1D. Here, we investigated how exercise signals β cells in T1D condition. For this, we used several approaches. Wild-type and IL-6 knockout (KO) C57BL/6 mice were exercised. Afterward, islets from control and trained mice were exposed to inflammatory cytokines (IL-1β plus IFN-γ). Islets from control mice and β-cell lines (INS-1E and MIN6) were incubated with serum from control or trained mice or medium obtained from 5-aminoimidazole-4 carboxamide1-β-d-ribofuranoside (AICAR)-treated C2C12 skeletal muscle cells. Subsequently, islets and β cells were exposed to IL-1β plus IFN-γ. Proteins were assessed by immunoblotting, apoptosis was determined by DNA-binding dye propidium iodide fluorescence, and NO(•) was estimated by nitrite. Exercise reduced 25, 75, and 50% of the IL-1β plus IFN-γ-induced iNOS, nitrite, and cleaved caspase-3 content, respectively, in pancreatic islets. Serum from trained mice and medium from AICAR-treated C2C12 cells reduced β-cell death, induced by IL-1β plus IFN-γ treatment, in 15 and 38%, respectively. This effect was lost in samples treated with IL-6 inhibitor or with serum from exercised IL-6 KO mice. In conclusion, muscle contraction signals β-cell survival in T1D through IL-6., (© FASEB.)

Endurance exercise training as well as leucine supplementation modulates glucose homeostasis and protein turnover in mammals. Here, we analyze whether leucine supplementation alters the effects of endurance exercise on these parameters in healthy mice. Mice were distributed into sedentary (C) and exercise (T) groups. The exercise group performed a 12-week swimming protocol. Half of the C and T mice, designated as the CL and TL groups, were supplemented with leucine (1.5 % dissolved in the drinking water) throughout the experiment. As well known, endurance exercise training reduced body weight and the retroperitoneal fat pad, increased soleus mass, increased VO2max, decreased muscle proteolysis, and ameliorated peripheral insulin sensitivity. Leucine supplementation had no effect on any of these parameters and worsened glucose tolerance in both CL and TL mice. In the soleus muscle of the T group, AS-160(Thr-642) (AKT substrate of 160 kDa) and AMPK(Thr-172) (AMP-Activated Protein Kinase) phosphorylation was increased by exercise in both basal and insulin-stimulated conditions, but it was reduced in TL mice with insulin stimulation compared with the T group. Akt phosphorylation was not affected by exercise but was lower in the CL group compared with the other groups. Leucine supplementation increased mTOR phosphorylation at basal conditions, whereas exercise reduced it in the presence of insulin, despite no alterations in protein synthesis. In trained groups, the total FoxO3a protein content and the mRNA for the specific isoforms E2 and E3 ligases were reduced. In conclusion, leucine supplementation did not potentiate the effects of endurance training on protein turnover, and it also reduced its positive effects on glucose homeostasis.

Background: The recreational use of anabolic-androgenic steroids (AAS) has reached alarming levels among healthy people. However, several complications have been related to consumption of these drugs, including liver disorders., Objective: To evaluate the prevalence of liver injuries in young Brazilian recreational AAS users., Methods: Between February/2007 and May/2012 asymptomatic bodybuilders who were ≥18 years old and reported AAS use for ≥6 months were enrolled. All had clinical evaluations, abdominal ultrasound (AUS), and blood tests., Results: 182 individuals were included in the study. The median age (interquartile range) was 26.0 years (22.0-30.0) and all were male. Elevated liver enzyme levels were observed in 38.5% (n = 70) of AAS users, and creatine phosphokinase was normal in 27.1% (n = 19) of them. Hepatic steatosis was observed by AUS in 12.1% of the sample. One individual had focal nodular hyperplasia and another had hepatocellular adenoma. One case each of hepatitis B and C virus infection was found. A diagnosis of toxic liver injury was suggested in 23 (12.6%) AAS users without a history of alcohol or other medications/drugs consumption, or evidence of other liver diseases., Conclusions/importance: Young Brazilian recreational AAS users presented a wide spectrum of liver injuries that included hepatotoxicity, fatty liver, and liver neoplasm. They also presented risk factors for liver diseases such as alcohol consumption and hepatitis B and C virus infection. The results suggest that the risk of AAS use for the liver may be greater than the esthetic benefits, and demonstrate the importance of screening AAS users for liver injuries.

Anabolic-androgenic steroids (AAS) are used to enhance physical performance and/or appearance. The aim of this study was to evaluate the influence of the concomitant use of alcohol, tobacco, cocaine, and AAS on blood lipid profiles of 145 asymptomatic male bodybuilders from the Northeast region of Brazil. Interviews, clinical exams, and serological evaluations were performed on all participants between 2007 and 2009. All subjects' self-reported use of testosterone or its derivatives, 118 individuals reported alcohol intake, 27-reported cigarette smoking, and 33 confirmed cocaine use. Four subjects were users of all drugs at the same time. Higher levels of total cholesterol and LDL-cholesterol were observed among concomitant users of alcohol, tobacco, cocaine, and AAS. The study's limitations are noted.

Background & Aims: Obese protein malnourished mice display liver insulin resistance and taurine (TAU) seems to attenuate this effect. The association between early-life malnutrition and hepatic redox balance in diet-induced insulin resistance is unknown. We investigated TAU supplementation effects upon liver redox state and insulin signalling in obese protein malnourished mice., Methods: Weaned male C57BL-6 mice were fed a control (14% protein - C) or a protein-restricted diet (6% protein - R) for 6 weeks. Afterwards, mice received a high-fat diet (34% fat - HFD) for 8 weeks (CH - RH). Half of the HFD-mice were supplemented with TAU (5%) throughout the treatment (CHT - RHT). Body and tissues' weight, respiratory quotient (RQ), glucose tolerance and insulin sensitivity, hepatic oxidant and antioxidant markers and insulin cascade proteins were assessed., Results: Protein restriction leads to typical features whereas HFD was able to induce a catch-up growth in RH. HFD-groups showed higher energy intake and adiposity, lower energy expenditure and altered RQ. Glucose tolerance and insulin sensitivity were impaired in HFD-groups and TAU attenuated these effects. H2 O2 content was increased in CHT and RHT despite no differences in antioxidant enzymes and GSH concentration. AKT and PTEN phosphorylation were significantly increased in CHT but not in RHT., Conclusion: Our data provide evidence for an association between TAU-induced improved glycaemic control because of PTEN inactivation and higher AKT phosphorylation. These effects seem to be related with altered hepatic redox balance in obese mice, and this effect is impaired by protein malnutrition., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The mitochondrial redox state plays a central role in the link between mitochondrial overloading and insulin resistance. However, the mechanism by which the ROS induce insulin resistance in skeletal muscle cells is not completely understood. We examined the association between mitochondrial function and H2O2 production in insulin resistant cells. Our hypothesis is that the low mitochondrial oxygen consumption leads to elevated ROS production by a mechanism associated with reduced PGC1α transcription and low content of phosphorylated CREB. The cells were transfected with either the encoded sequence for catalase overexpression or the specific siRNA for catalase inhibition. After transfection, myotubes were incubated with palmitic acid (500μM) and the insulin response, as well as mitochondrial function and fatty acid metabolism, was determined. The low mitochondrial oxygen consumption led to elevated ROS production by a mechanism associated with β-oxidation of fatty acids. Rotenone was observed to reduce the ratio of ROS production. The elevated H2O2 production markedly decreased the PGC1α transcription, an effect that was accompanied by a reduced phosphorylation of Akt and CREB. The catalase transfection prevented the reduction in the phosphorylated level of Akt and upregulated the levels of phosphorylated CREB. The mitochondrial function was elevated and H2O2 production reduced, thus increasing the insulin sensitivity. The catalase overexpression improved mitochondrial respiration protecting the cells from fatty acid-induced, insulin resistance. This effect indicates that control of hydrogen peroxide production regulates the mitochondrial respiration preventing the insulin resistance in skeletal muscle cells by a mechanism associated with CREB phosphorylation and β-oxidation of fatty acids., (Copyright © 2013 Elsevier B.V. All rights reserved.)

We herein studied the role of glutamate dehydrogenase (GDH), in response to leucine (LEU) supplementation, upon insulin secretion of malnourished rats. Weaned male Wistar rats were fed normal-protein (17%) or low-protein diet (6%, LP) for 8 weeks. Half of the rats of each group were supplemented with LEU (1.5%) in the drinking water for the following 4 weeks. Gene and protein expressions, static insulin secretion, and cytoplasmic Ca(2+) oscillations were measured. Glutamate dehydrogenase messenger RNA was 58% lower in LP islets, and LEU supplementation augmented it in 28%. The LP islets secreted less insulin when exposed to 20 mmol/L LEU, 20 mmol/L LEU + 2 mmol/L glutamine (with or without 5 mmol/L aminooxyacetic acid, a branched chain aminotransferase inhibitor, or 20 μmol/L epigallocatechin gallate, a GDH inhibitor), 20 mmol/L α-ketoisocaproate, glutamine + 20 mmol/L β-2-aminobicyclo[2.2.1]heptane-2-carboxylic acid (a GDH activator), and 22.2 mmol/L glucose. Leucine supplementation augmented insulin secretion to levels found in normal-protein islets in all the above conditions, an effect that was blunted when islets were incubated with epigallocatechin gallate. The glutamine + β-2-aminobicyclo[2.2.1]heptane-2-carboxylic acid-induced increased [Ca(2+)](i) and oscillations were higher than those for LP islets. Leucine supplementation normalized these parameters in LP islets. Impaired GDH function was associated with lower insulin release in LP islets, and LEU supplementation normalized insulin secretion via restoration of GDH function. In addition, GDH may contribute to insulin secretion through ameliorations of Ca(2+) handling in LP islets., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Endurance training has been shown to increase pancreatic β-cell function and mass. However, whether exercise modulates β-cell growth and survival pathways signaling is not completely understood. This study investigated the effects of exercise on growth and apoptotic markers levels in rat pancreatic islets. Male Wistar rats were randomly assigned to 8-wk endurance training or to a sedentary control group. After that, pancreatic islets were isolated; gene expression and the total content and phosphorylation of several proteins related to growth and apoptotic pathways as well as the main antioxidant enzymes were determined by real-time polymerase chain reaction and Western blot analysis, respectively. Reactive oxygen species (ROS) production was measured by fluorescence. Endurance training increased the time to reach fatigue by 50%. Endurance training resulted in increased protein phosphorylation content of AKT (75%), AKT substrate (AS160; 100%), mTOR (60%), p70s6k (90%), and ERK1/2 (50%), compared with islets from control group. Catalase protein content was 50% higher, whereas ROS production was 49 and 77% lower in islets from trained rats under basal and stimulating glucose conditions, respectively. Bcl-2 mRNA and protein levels increased by 46 and 100%, respectively. Bax and cleaved caspase-3 protein contents were reduced by 25 and 50% in islets from trained rats, respectively. In conclusion, these results demonstrate that endurance training favors the β-cell growth and survival by activating AKT and ERK1/2 pathways, enhancing antioxidant capacity, and reducing ROS production and apoptotic proteins content.

Endurance exercise has been shown to reduce pancreatic islets glucose-stimulated insulin secretion (GSIS). Anaplerotic/cataplerotic pathways are directly related to GSIS signaling. However, the effect of endurance training upon pancreatic islets anaplerotic enzymes is still unknown. In this sense, we tested the hypothesis that endurance exercise decreases GSIS by reducing anaplerotic/cataplerotic enzymes content. Male Wistar rats were randomly assigned to one of the four experimental groups as follows: control sedentary group (CTL), trained 1 day per week (TRE1×), trained 3 days per week (TRE3×) and trained 5 days per week (TRE5x) and submitted to an 8 weeks endurance-training protocol. After the training protocol, pancreatic islets were isolated and incubated with basal (2.8 mM) and stimulating (16.7 mM) glucose concentrations for GSIS measurement by radioimmunoassay. In addition, pyruvate carboxylase (PYC), pyruvate dehydrogenase (PDH), pyruvate dehydrogenase kinase 4 (PDK4), ATP-citrate lyase (ACL) and glutamate dehydrogenase (GDH) content were quantified by western blotting. Our data showed that 8 weeks of chronic endurance exercise reduced GSIS by 50% in a dose-response manner according to weekly exercise frequency. PYC showed significant twofold increase in TRE3×. PYC enhancement was even higher in TRE5× (p < 0.0001). PDH and PDK4 reached significant 25 and 50% enhancement, respectively compared with CTL. ACL and GDH also reported significant 50 and 75% increase, respectively. The absence of exercise-induced correlations among GSIS and anaplerotic/cataplerotic enzymes suggests that exercise may control insulin release by activating other signaling pathways. The observed anaplerotic and cataplerotic enzymes enhancement might be related to β-cell surviving rather than insulin secretion.

The glucose-fatty acid cycle explains the preference for fatty acid during moderate and long duration physical exercise. In contrast, there is a high glucose availability and oxidation rate in response to intense physical exercise. The reactive oxygen species (ROS) production during physical exercise suggests that the redox balance is important to regulate of lipids/carbohydrate metabolism. ROS reduces the activity of the Krebs cycle, and increases the activity of mitochondrial uncoupling proteins. The opposite effects happen during moderate physical activity. Thus, some issues is highlighted in the present review: Why does skeletal muscle prefer lipids in the basal and during moderate physical activity? Why does glucose-fatty acid fail to carry out their effects during intense physical exercise? How skeletal muscles regulate the lipids and carbohydrate metabolism during the contraction-relaxation cycle?

Type 2 diabetes mellitus results from the complex association of insulin resistance and pancreatic β-cell failure. Obesity is the main risk factor for type 2 diabetes mellitus, and recent studies have shown that, in diet-induced obesity, the hypothalamus becomes inflamed and dysfunctional, resulting in the loss of the perfect coupling between caloric intake and energy expenditure. Because pancreatic β-cell function is, in part, under the control of the autonomic nervous system, we evaluated the role of hypothalamic inflammation in pancreatic islet function. In diet-induced obesity, the earliest markers of hypothalamic inflammation are present at 8 weeks after the beginning of the high fat diet; similarly, the loss of the first phase of insulin secretion is detected at the same time point and is restored following sympathectomy. Intracerebroventricular injection of a low dose of tumor necrosis factor α leads to a dysfunctional increase in insulin secretion and activates the expression of a number of markers of apoptosis in pancreatic islets. In addition, the injection of stearic acid intracerebroventricularly, which leads to hypothalamic inflammation through the activation of tau-like receptor-4 and endoplasmic reticulum stress, produces an impairment of insulin secretion, accompanied by increased expression of markers of apoptosis. The defective insulin secretion, in this case, is partially dependent on sympathetic signal-induced peroxisome proliferator receptor-γ coactivator Δα and uncoupling protein-2 expression and is restored after sympathectomy or following PGC1α expression inhibition by an antisense oligonucleotide. Thus, the autonomic signals generated in concert with hypothalamic inflammation can impair pancreatic islet function, a phenomenon that may explain the early link between obesity and defective insulin secretion.

Background: Industrial toxin and drugs have been associated with non-alcoholic fatty liver disease (NAFLD); in these cases, the disease has been termed toxicant-associated steatohepatitis (TASH)., Aim: This study hypothesizes that the use of anabolic-androgenic steroids (AAS) could also be a risk factor to TASH or better toxicant-associated fatty liver disease (TAFLD) development., Methodology: Case-control study including 180 non-competitive recreational male bodybuilders from August/2007 to March/2009. Ninety-five had a history of intramuscular AAS use (cases; G1) and 85 were non-users (controls; G2). They underwent a clinical evaluation and abdominal ultrasound, and their blood levels of aminotransferases, creatine phosphokinase (CPK), lipids, glucose and insulin were measured. TAFLD criteria: history of AAS use >2 years; presence of hepatic steatosis on ultrasound and/or aminotransferase alterations with normal CPK levels; exclusion of ethanol intake ≥20 g/day or use of other drugs; and exclusion of obesity, dyslipidaemia, diabetes and other liver diseases. Homeostasis model assessment for insulin resistance ≥3 was considered insulin resistant. Independent t-test, odds ratio (OR) and 95% confidence intervals (95% CI) were calculated., Results: All cases were asymptomatic. Clinical and laboratorial data were similar in G1 and G2 (P>0.05). TAFLD criteria were observed in 12.6% of the G1 cases and 2.4% of controls had criteria compliant with non-alcoholic fatty liver related to metabolic conditions. OR was 6.0 (95% CI: 1.3-27.6)., Conclusions: These results suggest that AAS could be a possible new risk factor for TAFLD. In this type of fatty liver disease, the individuals had a low body fat mass and they did not present insulin resistance., (© 2010 John Wiley & Sons A/S.)

Endurance exercise is known to enhance peripheral insulin sensitivity and reduce insulin secretion. However, it is unknown whether the latter effect is due to the reduction in plasma substrate availability or alterations in β-cell secretory machinery. Here, we tested the hypothesis that endurance exercise reduces insulin secretion by altering the intracellular energy-sensitive AMP-activated kinase (AMPK) signaling pathway. Male Wistar rats were submitted to endurance protocol training one, three, or five times per week, over 8 weeks. After that, pancreatic islets were isolated, and glucose-induced insulin secretion (GIIS), glucose transporter 2 (GLUT2) protein content, total and phosphorylated calmodulin kinase kinase (CaMKII), and AMPK levels as well as peroxisome proliferator-activated receptor-γ coactivator-1-α (PGC-1α) and uncoupling protein 2 (UCP2) content were measured. After 8 weeks, chronic endurance exercise reduced GIIS in a dose-response manner proportionally to weekly exercise frequency. Contrariwise, increases in GLUT2 protein content, CaMKII and AMPK phosphorylation levels were observed. These alterations were accompanied by an increase in UCP2 content, probably mediated by an enhancement in PGC-1α protein expression. In conclusion, chronic endurance exercise induces adaptations in β-cells leading to a reduction in GIIS, probably by activating the AMPK signaling pathway.

Low-protein diet impairs insulin secretion in response to nutrients and may induce several metabolic disorders including diabetes, obesity, and cardiovascular disease. In the present study, the influence of leucine supplementation on glutamate dehydrogenase (GDH) expression and glucose-induced insulin secretion (GIIS) was investigated in malnourished rats. Four groups were fed with different diets for 12 weeks: a normal-protein diet (17%) without or with leucine supplementation or a low (6%)-protein diet without (LP) or with leucine supplementation (LPL). Leucine (1.5%) was supplied in the drinking water. Western blotting analysis revealed reduced GDH expression in LP, whereas LPL displayed improved GDH expression, similar to control. The GIIS and leucine-induced insulin release were also enhanced in LPL compared with LP and similar to those observed in rats fed a normal-protein diet without leucine supplementation. In addition, GDH allosteric activators produced an increased insulin secretion in LPL. These findings indicate that leucine supplementation was able to increase GDH expression leading to GIIS restoration, probably by improved leucine metabolic pathways., (Copyright 2010 Elsevier Inc. All rights reserved.)

Pancreatic beta-cells and skeletal muscle act in a synergic way in the control of systemic glucose homeostasis. Several pyruvate-dependent and -independent shuttles enhance tricarboxylic acid cycle intermediate (TACI) anaplerosis and increase beta-cell ATP:ADP ratio, triggering insulin exocytotic mechanisms. In addition, mitochondrial TACI cataplerosis gives rise to the so-called metabolic coupling factors, which are also related to insulin release. Peripheral insulin resistance seems to be related to skeletal muscle fatty acid (FA) accumulation and oxidation imbalance. In this sense, exercise has been shown to enhance skeletal muscle TACI anaplerosis, increasing FA oxidation and by this manner restores insulin sensitivity. Protein malnutrition reduces beta-cell insulin synthesis, release and peripheral sensitivity. Despite little available data concerning mitochondrial metabolism under protein malnutrition, evidence points towards reduced beta-cell and skeletal muscle mitochondrial capacity. The observed decrease in insulin synthesis and release may reflect reduced anaplerotic and cataplerotic capacity. Furthermore, insulin release is tightly coupled to ATP:ADP rise which in turn is related to TACI anaplerosis. The effect of protein malnutrition upon peripheral insulin resistance is time-dependent and directly related to FA oxidation capacity. In contrast to beta-cells, TACI anaplerosis and cataplerosis pathways in skeletal muscle seem to control FA oxidation and regulate insulin resistance.

Predicting one repetition maximum equations accuracy in paralympic rowers Resistance training intensity is prescribed using percentiles of the maximum strength, defined as the maximum tension generated for a muscle or muscular group. This value is found through the application of the one maximal repetition (1RM) test. One maximal repetition test demands time and still is not appropriate for some populations because of the risk it offers. In recent years, the prediction of maximal strength, through predicting equations, has been used to prevent the inconveniences of the 1RM test. The purpose of this study was to verify the accuracy of 12 1RM predicting equations for disabled rowers. Nine male paralympic rowers (7 one-leg amputated rowers and 2 cerebral paralyzed rowers; age, 30 +/- 7.9 years; height, 175.1 +/- 5.9 cm; weight, 69 +/- 13.6 kg) performed 1RM test for lying T-bar row and flat barbell bench press exercises to determine upper-body strength and leg press exercise to determine lower-body strength. One maximal repetition test was performed, and based on submaximal repetitions loads, several linear and exponential equations models were tested with regard of their accuracy. We did not find statistical differences for lying T-bar row and bench press exercises between measured and predicted 1RM values (p = 0.84 and 0.23 for lying T-bar row and flat barbell bench press, respectively); however, leg press exercise reached a high significant difference between measured and predicted values (p < 0.01). In conclusion, rowers with motor disabilities tolerate 1RM testing procedures, and predicting 1RM equations are accurate for bench press and lying T-bar row, but not for leg press, in this kind of athlete.

Background: Aerobic exercise is an important ally in the fight against cardiovascular risk factors. However, the effects of high-intensity exercise on these factors are still poorly known., Objective: To compare the effects of aerobic and anaerobic exercise protocols on cardiac risk factors., Methods: 22 individuals with mean age of 40+/-8 years were distributed into the following groups: control (CO), endurance training (ET) and interval training (IT). The protocols lasted 12 weeks, three times a week, with intensities of 10% below and 20% above the anaerobic threshold (AnT). The following measurements were taken: total body mass (TBM), body mass index (BMI), waist circumference (WC), hip circumference (HC), and body composition, in addition to plasma concentrations of glucose (GLU), total cholesterol (CHO), and triglycerides (TG). Waist-hip ratio (WHR) and conicity index (C index) were also calculated., Results: The TBM, BMI, WC, GLU, and body composition variables showed significant changes in the ET and IT groups. CHO and HC values were significantly reduced in the ET group, whereas WHR showed a significant reduction in the IT group. AnT and C index in the IT group were significantly different in relation to ET., Conclusion: In view of the differences found in the results of the variables studied in relation to the training performed, we conclude that an exercise program that includes both high and low-intensity activities is more efficient to ensure the reduction of a greater number of cardiac risk variables.

The purpose of this study was to characterize aerobic, anaerobic, handgrip strength, and body fat content (BF) characteristics in paralympic rowers (ROW) in order to determine motor disabled rowers' fitness level and if specific motor disabilities could impair performance in this specific population. Upper body anaerobic threshold (LacT), peak (PK-AnP), mean (M-AnP), and lower (L-AnP) anaerobic power, peak anaerobic power to weight ratio (RelPk-AnP) and fatigue index (FI) were measured by the Wingate test (WinT). Handgrip strength was also measured and skinfold sum was used to estimate BF and were compared with a reference group of recreational disabled athletes (CON). LacT was significantly higher (p < 0.01) in ROW compared with CON. RelPk-AnP and BF were significantly different (p < 0.05) in ROW compared with CON as well. All other measured parameters did not significantly differ between ROW and CON. In most of cases, rowers have shown a relative low performance level, induced probably by specific disabilities.

Maximal blood lactate steady state concentration (MLSS) and anaerobic threshold (AT) have been shown to accurately predict long distance events performance and training loads, as well, in human athletes. Horse endurance races can take up to 160 km and, in practice, coaches use the 4 mM blood lactate concentration, a human based fixed concentration to establish AT, to predict training loads to horse athletes, what can lead to misleading training loads. The lactate minimum speed (LMS) protocol that consists in an initial elevation in blood lactate level by a high intensity bout of exercise and then establishes an individual equilibrium between lactate production and catabolism during progressive submaximal efforts, has been proposed as a nonfixed lactate concentration, to measure individual AT and at the same time predicts MLSS for human long distance runners and basketball players as well. The purpose of this study was to determine the reliability of the LMS protocol in endurance horse athletes. Five male horses that were engaged on endurance training, for at least 1 year of regular training and competition, were used in this study. Animals were submitted to a 500 m full gallop to determine each blood lactate time to peak (LP) after these determinations, animals were submitted to a progressive 1000 m exercise, starting at 15 km h(-1) to determine LMS, and after LMS determination animals were also submitted to two 10,000 m running, first at LMS and then 10% above LMS to test MLSS accuracy. Mean LP was 8.2+/-0.7 mM at approximately 5.8+/-6.09 min, mean LMS was 20.75+/-2.06 km h(-1) and mean heart rate at LMS was 124.8+/-4.7 BPM. Blood lactate remained at rest baseline levels during 10,000 m trial at LMS, but reached a six fold significantly raise during 10% above LMS trial after 4000 and 6000 m (p<0.05) and (p<0.01) after 8000 and 10,000 m. In conclusion, our adapted LMS protocol for horse athletes proposed here seems to be a reliable method to state endurance horse athletes LT and MLSS.

Exercise training is known to induce an increase in free radical production potentially leading to enhanced muscle injury. Vitamins C and E are well known antioxidants that may prevent muscle cell damage. The purpose of this study was to determine the effects of these supplemental antioxidant vitamins on markers of oxidative stress, muscle damage and performance of elite soccer players. Ten male young soccer players were divided into two groups. Supplementation group (n = 5) received vitamins C and E supplementation daily during the pre-competitive season (S group), while the placebo group (PL group, n = 5) received a pill containing maltodextrin. Both groups performed the same training load during the three-month pre-season training period. Erythrocyte antioxidant enzymes glutathione reductase, catalase and plasma carbonyl derivatives did not show any significant variation among the experimental groups. Similarly, fitness level markers did not differ among the experimental groups. However, S group demonstrated lower lipid peroxidation and muscle damage levels (p < 0.05) compared to PL group at the final phase of pre-competitive season. In conclusion, our data demonstrated that vitamin C and E supplementation in soccer players may reduce lipid peroxidation and muscle damage during high intensity efforts, but did not enhance performance.

Given the potential of reactive oxygen species to damage intracellular proteins during subsequent bouts of muscle contractions, it was suggested that, when this production exceeds the antioxidant capacity, the preexisting antioxidant pathways may be complemented by the synthesis of the defense mechanism represented by heat shock proteins (HSPs), stress proteins with the function of repair and maintaining protein folding. To test this hypothesis, we analyzed reactive carbonyl derivatives in plasma and the expression of HSP72 and activities of enzymes from the oxidative and antioxidant defense systems in the soleus muscle of sedentary rats and rats trained by two protocols: continuous and intermittent. We analyzed all three groups at rest and 2 h after acute exercise. After 8 wk of training, the animals from both groups clearly demonstrated higher resistance to exercise. Both trained groups showed significantly higher citrate synthase, catalase, and glutathione reductase activities than the control group (P < 0.01). After acute exercise, catalase and glutathione reductase activities significantly decreased (P < 0.01) and plasma reactive carbonyl derivatives significantly increased (P < 0.05) in the sedentary group, suggesting an oxidative-stress condition as responsible for exhaustion in this group. Finally, after acute exercise, the induction of HSP72 expression occurred only in the sedentary group, suggesting that HSP72 acts as a complementary protective mechanism in exercise-induced oxidative stress.