Metabolomics Reveals Relationship between Plasma Inositols and Birth Weight: Possible Markers for Fetal Programming of Type 2 Diabetes

Epidemiological studies in man and with experimental animal models have shown that intrauterine growth restriction (IUGR) resulting in low birth weight is associated with higher risk of programming welfare diseases in later life. In the pig, severe IUGR occurs naturally and contribute substantially to a large intralitter variation in birth weight and may therefore be a good model for man. In the present paper the natural form of IUGR in pigs was studied close to term by nuclear magnetic resonance (NMR-)based metabolomics. The NMR-based investigations revealed different metabolic profiles of plasma samples from low-birth weight (LW) and high-birth weight (HW) piglets, respectively, and differences were assigned to levels of glucose and myo-inositol. Further studies by GC-MS revealed that LW piglets had a significant higher concentration of myoinositol and D-chiro-inositol in plasma compared to larger littermates. Myo-inositol and D-chiro-inositol have been coupled with glucose intolerance and insulin resistance in adults, and the present paper therefore suggests that IUGR is related to impaired glucose metabolism during fetal development, which may cause type 2 diabetes in adulthood

Phytanic acid stimulates glucose uptake in a model of skeletal muscles, the primary porcine myotubes

BACKGROUND: Phytanic acid (PA) is a chlorophyll metabolite with potentials in regulating glucose metabolism, as it is a natural ligand of the peroxisome proliferator-activated receptor (PPAR) that is known to regulate hepatic glucose homeostasis. This study aimed to establish primary porcine myotubes as a model for measuring glucose uptake and glycogen synthesis, and to examine the impact of physiological amounts of PA on glucose uptake and glycogen synthesis either alone or in combination with insulin. METHODS: Porcine satellite cells were cultured into differentiated myotubes and tritiated 2-deoxyglucose (2-DOG) was used to measure glucose uptake, in relation to PA and 2-DOG exposure times and also in relation to PA and insulin concentrations. The MIXED procedure model of SAS was used for statistical analysis of data. RESULTS: PA increased glucose uptake by approximately 35%, and the presence of insulin further increased the uptake, but this further increase in uptake was non- additive and less pronounced at high insulin concentrations. There was no effect of PA alone on glycogen synthesis, while the insulin stimulation of glycogen was increased by 20% in the presence of PA. PA neither stimulated glucose uptake nor glycogen synthesis in insulin-resistant myotubes generated by excess glucose exposure. CONCLUSIONS: Primary porcine myotubes were established as a model of skeletal muscles for measuring glucose uptake and glycogen synthesis, and we showed that PA can play a role in stimulating glucose uptake at no or inadequate insulin concentrations

Feasibility and acceptability of electronic symptom surveillance with clinician feedback using the Patient-Reported Outcomes version of Common Terminology Criteria for Adverse Events (PRO-CTCAE) in Danish prostate cancer patients

Abstract Background The aim was to examine the feasibility, acceptability and clinical utility of electronic symptom surveillance with clinician feedback using a subset of items drawn from the Patient-Reported Outcomes version of Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a cancer treatment setting. Methods Danish-speaking men with castration-resistant metastatic prostate cancer receiving treatment at the Department of Oncology, Rigshospitalet, Copenhagen between March 9, 2015 and June 8, 2015 were invited to participate (n = 63 eligible). Participants completed the PRO-CTCAE questionnaire on tablet computers using AmbuFlex software at each treatment visit in the outpatient clinic. In total, 22 symptomatic toxicities (41 PRO-CTCAE items), corresponding to the symptomatic adverse-events profile associated with the regimens commonly used for prostate cancer treatment (Docetaxel, Cabazitaxel, Abiraterone, Alpharadin), were selected. Participants’ PRO-CTCAE responses were presented graphically to their treating oncologists via an AmbuFlex dashboard, for real-time use to enhance the patient-clinician dialogue that occurs during the consultation prior to each treatment cycle. Technical and clinical barriers and acceptability were evaluated through semi-structured interviews with both patients and oncologists. Patients receiving active treatment at the end of the study period completed an evaluation questionnaire. Results Fifty-four out of sixty-three (86%) eligible patients were enrolled. The PRO-CTCAE questionnaire was completed a total of 168 times by 54 participants (median number per patient was 3, range 1–5). Eight surveys were missed, resulting in a compliance rate of 97%. At the end of the study period, 35 patients (65%) were still receiving active treatment and completed the evaluation questionnaire. Patients reported that their PRO-CTCAE responses served as a communication tool. Oncologists stated that the availability of the PRO-CTCAE self-reports during the consultation improved patient-clinician communication about side effects. Conclusion Electronic capture of symptomatic toxicities using PRO-CTCAE and the submission of self-reports to clinicians prior to consultation were feasible among metastatic prostate cancer patients receiving chemotherapy in an outpatient setting, and this procedure was acceptable to both patients and clinicians. Continued research, including a cluster-randomized trial, will evaluate the effects of submitting patients’ PRO-CTCAE results to clinicians prior to consultation on the quality of side-effects management and resultant clinical outcomes

Naringenin and falcarinol stimulate glucose uptake and TBC1D1 phosphorylation in porcine myotube cultures

Abstract: Insulin resistance in muscles is a major problem associated with Type 2 diabetes. Bioactive compounds of plant origin have long been known for possessing anti-diabetic properties. We have studied the effect of the bioactive compounds naringenin (dihydroflavonol) and falcarinol (polyacetylene) on glucose uptake (GU) in normal and insulin resistant primary porcine myotubes, in the presence and absence of insulin to identify signaling pathways mediating their effects on GU. The dependence on glucose transporter type 4 (Glut4) activity, insulin signaling and AMP-activated protein kinase (AMPK)-signaling was studied by using the Glut4 inhibitor indinavir, the phosphatidyl inositol-3 kinase (PI3K) and p38 mitogen activated protein kinase (MAPK) inhibitor wortmannin, and the AMPK inhibitor dorsomorphin (DM), respectively. Naringenin and falcarinol stimulated GU was attenuated in the presence of indinavir and wortmannin, indicating a dependence on Glut4 activity as well as PI3K and/or p38MAPK activity. By contrast, DM diminished GU induced by naringenin only, indicating that falcarinol-stimulated GU was independent of AMPK activity. Finally, we show that naringenin and falcarinol enhance phosphorylation of TBC1D1 suggesting that these compounds enhance translocation of Glut4 containing vesicles and thereby GU via a TBC1D1-dependent mechanism

Post-mortem activity of the glycogen debranching enzyme and change in the glycogen pools in porcine M. longissimus dorsi from carriers and non-carriers of the RN− gene

Glycogen debranching enzyme (GDE) is together with glycogen phosphorylase responsible for the degradation of glycogen. The present study compares the post-mortem activity of GDE and breakdown of the glycogen pools in M. longissimus dorsi of RN- carrier pigs and in wild type animals. The activity of GDE (n=14) and pH (n=20) was measured 0.5, 3, 5, 24 and 48 h post-mortem. The change in pro-glycogen and in macro-glycogen content (n=20) was followed until 216 h post-mortem and the transcription level of GDE, glycogenin and glycogen synthase m-RNA (n=19) were measured 0.5 h post-mortem. Both the activity of GDE and the transcription level of GDE were found to be similar in RN- carriers and wild type animals shortly after slaughter. However, the activity declined faster in wild type animals compared with RN- carriers with increasing time post-mortem. The contents of both pro-glycogen and macro-glycogen were higher in RN- carriers compared with wild type animals, and further, the proportion of macro-glycogen was higher in RN- carriers compared with wild type animals. During the post-mortem period, only degradation of pro-glycogen was observed in both genotypes. The decrease in pH was faster and the ultimate pH lower in RN- carriers than in wild type animals. It was suggested that the higher GDE activity in the late phase of the post-mortem period in muscles from RN- carriers renders the extended pH decrease in these muscles

Efectos y beneficios del entrenamiento de fuerza en pacientes con cáncer: revisión sistemática de la literatura

Introduction: cancer is among the diseases having the greatest mortality rates and the cause of many disabilities worldwide. The practice of exercise is developed as an adjuvant therapy along with the cancer treatment to reduce mortality and disability in the different types of cancer.Objective: to identify the effects of strength training on cancer patients.Methods: a complete review of the medical literature was conducted until December 2018, scientific articles published in indexed bases from 2015 to 2018. The studies included were in population over 18 years old with cancer diagnosis regardless of sociodemographic characteristics, type or stage of cancer. The data extracted were on the population, intervention and control groups, type of cancer, period, frequency of intervention and results.Results: during the first search 36071 titles of clinical study were found in specialized journals. 10 experimental studies were chosen. Multiple positive effects were found, as well as components that should be taken into account when performing strength training on cancer patients or cancer survivors.Conclusions: strength training in patients with cancer or survivors of this disease, helps them to improve their symptoms as well as their quality of life, strength, improved mobility and pain, among others. Also, strength training is beneficial to patients without causing adverse effects or long-term complications.Introducción: El cáncer se encuentra entre las enfermedades con mayor mortalidad y causante de un gran número de discapacidades a nivel mundial. El ejercicio surge como un coadyuvante del tratamiento oncológico para disminuir la mortalidad y discapacidad en los diferentes tipos de cáncer.Objetivo: Identificar los efectos del entrenamiento de fuerza en pacientes con cáncer.Método:  Se realizó una revisión de la literatura hasta diciembre del 2018, de artículos científicos publicados en bases de indexadas desde 2015 y hasta 2018. Los estudios incluidos fueron en población mayor a 18 años con diagnóstico de cáncer sin importar características sociodemográficas, tipo o estadio del cáncer. Los datos extraídos fueron sobre la población, grupos de intervención y control, tipo de cáncer, periodo, frecuencia de la intervención y resultados.Resultados: Durante la primera búsqueda 36071 títulos de estudios clínicos fueron encontrados en revistas especializadas. Al final 10 estudios de carácter experimental fueron seleccionados. En dichos estudios, múltiples efectos fueron encontrados, así como componentes que se deben tener en cuenta a realizar un entrenamiento de fuerza en pacientes con cáncer o sobrevivientes del mismo.Conclusiones: El entrenamiento de fuerza en pacientes con cáncer o sobrevivientes de esta enfermedad, les ayuda a mejorar su sintomatología al igual que su calidad de vida, fatiga, fuerza, mejoría en la movilidad y el dolor, entre otros. Así mismo, el entrenamiento de fuerza es beneficioso para los pacientes sin causar efectos adversos o complicaciones a largo plazo

Creatine-induced activation of antioxidative defence in myotube cultures revealed by explorative NMR-based metabonomics and proteomics

<p>Abstract</p> <p>Background</p> <p>Creatine is a key intermediate in energy metabolism and supplementation of creatine has been used for increasing muscle mass, strength and endurance. Creatine supplementation has also been reported to trigger the skeletal muscle expression of insulin like growth factor I, to increase the fat-free mass and improve cognition in elderly, and more explorative approaches like transcriptomics has revealed additional information. The aim of the present study was to reveal additional insight into the biochemical effects of creatine supplementation at the protein and metabolite level by integrating the explorative techniques, proteomics and NMR metabonomics, in a systems biology approach.</p> <p>Methods</p> <p>Differentiated mouse myotube cultures (C2C12) were exposed to 5 mM creatine monohydrate (CMH) for 24 hours. For proteomics studies, lysed myotubes were analyzed in single 2-DGE gels where the first dimension of protein separation was pI 5-8 and second dimension was a 12.5% Criterion gel. Differentially expressed protein spots of significance were excised from the gel, desalted and identified by peptide mass fingerprinting using MALDI-TOF MS. For NMR metabonomic studies, chloroform/methanol extractions of the myotubes were subjected to one-dimensional ¹H NMR spectroscopy and the intracellular oxidative status of myotubes was assessed by intracellular DCFH₂oxidation after 24 h pre-incubation with CMH.</p> <p>Results</p> <p>The identified differentially expressed proteins included vimentin, malate dehydrogenase, peroxiredoxin, thioredoxin dependent peroxide reductase, and 75 kDa and 78 kDa glucose regulated protein precursors. After CMH exposure, up-regulated proteomic spots correlated positively with the NMR signals from creatine, while down-regulated proteomic spots were negatively correlated with these NMR signals. The identified differentially regulated proteins were related to energy metabolism, glucose regulated stress, cellular structure and the antioxidative defence system. The suggested improvement of the antioxidative defence was confirmed by a reduced intracellular DCFH₂oxidation with increasing concentrations of CMH in the 24 h pre-incubation medium.</p> <p>Conclusions</p> <p>The explorative approach of this study combined with the determination of a decreased intracellular DCFH₂oxidation revealed an additional stimulation of cellular antioxidative mechanisms when myotubes were exposed to CMH. This may contribute to an increased exercise performance mediated by increased ability to cope with training-induced increases in oxidative stress.</p