RESUMEN
In the last few decades, there has been increasing social awareness for environmental conservation, which is driving the development of composite materials based on natural fibers. These new materials have interesting properties that allow for their use in a variety of applications. This study deals with the development of composite materials based on unsaturated polyester resins reinforced with recycled mineral fibers, such as slate fibers obtained from slate production waste, which have similar properties to glass fiber. The mechanical properties of these composites have been determined by tensile and flexural/bending tests. The influence of various variables such as matrix composition (flexible polyester content) and the weight percentage of fiber added to mechanical properties were evaluated. The flexible/rigid polyester content varied from 0 to 40% and the fiber one from 0 to 30 wt%. Composites with ≥20 wt% of slate fiber reinforcement are shown to have tensile (35 MPa) and flexural (57 MPa) strengths that can compete with materials reinforced with artificial fibers.
RESUMEN
Introduction: Many investigators have attempted to define the molecular nature of changes responsible for insulin resistance in muscle, but a molecular approach may not consider the overall physiological context of muscle. Because the energetic state of ATP (ΔGATP) could affect the rate of insulin-stimulated, energy-consuming processes, the present study was undertaken to determine whether the thermodynamic state of skeletal muscle can partially explain insulin sensitivity and fuel selection independently of molecular changes. Methods: 31P-MRS was used with glucose clamps, exercise studies, muscle biopsies and proteomics to measure insulin sensitivity, thermodynamic variables, mitochondrial protein content, and aerobic capacity in 16 volunteers. Results: After showing calibrated 31P-MRS measurements conformed to a linear electrical circuit model of muscle nonequilibrium thermodynamics, we used these measurements in multiple stepwise regression against rates of insulin-stimulated glucose disposal and fuel oxidation. Multiple linear regression analyses showed 53% of the variance in insulin sensitivity was explained by 1) VO2max (p = 0.001) and the 2) slope of the relationship of ΔGATP with the rate of oxidative phosphorylation (p = 0.007). This slope represents conductance in the linear model (functional content of mitochondria). Mitochondrial protein content from proteomics was an independent predictor of fractional fat oxidation during mild exercise (R2 = 0.55, p = 0.001). Conclusion: Higher mitochondrial functional content is related to the ability of skeletal muscle to maintain a greater ΔGATP, which may lead to faster rates of insulin-stimulated processes. Mitochondrial protein content per se can explain fractional fat oxidation during mild exercise.
RESUMEN
Background: Resting skeletal muscle in insulin resistance prefers to oxidize carbohydrate rather than lipid, exhibiting metabolic inflexibility. Although this is established in resting muscle, complexities involved in directly measuring fuel oxidation using indirect calorimetry across a muscle bed have limited studies of this phenomenon in working skeletal muscle. During mild exercise and at rest, whole-body indirect calorimetry imperfectly estimates muscle fuel oxidation. We provide evidence that a method termed "ΔRER" can reasonably estimate fuel oxidation in skeletal muscle activated by exercise. Methods: Completely sedentary volunteers (n = 20, age 31 ± 2 years, VÌO2peak 24.4 ± 1.5 mL O2 per min/kg) underwent glucose clamps to determine insulin sensitivity and graded exercise consisting of three periods of mild steady-state cycle ergometry (15, 30, 45 watts, or 10%, 20%, and 30% of maximum power) with measurements of whole-body gas exchange. ΔRER, the RER in working muscle, was calculated as (VÌCO2exercise -VÌCO2rest)/(VÌO2exercise - VÌO2rest), from which the fraction of fuel accounted for by lipid was estimated. Results: Lactate levels were low and stable during steady-state exercise. Muscle biopsies were used to estimate mitochondrial content. The rise of VÌO2 at onset of exercise followed a monoexponential function, with a time constant of 51 ± 7 sec, typical of skeletal muscle; the average O2 cost of work was about 12 mL O2/watt/min, representing a mechanical efficiency of about 24%. At work rates of 30 or 45 watts, active muscle relied predominantly on carbohydrate, independent of insulin sensitivity within this group of very sedentary volunteers. Conclusions: The fraction of muscle fuel oxidation from fat was predicted by power output (P < 0.001) and citrate synthase activity (P < 0.05), indicating that low mitochondrial content may be the main driver of fuel choice in sedentary people, independent of insulin sensitivity.
Asunto(s)
Resistencia a la Insulina , Humanos , Adulto , Carbohidratos , Ejercicio Físico/fisiología , Músculo Esquelético/metabolismo , Lípidos , Consumo de OxígenoRESUMEN
Skeletal muscle is highly plastic and dynamically regulated by the body's physical demands. This study aimed to determine the plasticity of skeletal muscle DNA methylation in response to 8 weeks of supervised exercise training in volunteers with a range of insulin sensitivities. We studied 13 sedentary participants and performed euglycemic hyperinsulinemic clamps with basal vastus lateralis muscle biopsies and peak aerobic activity (VO2 peak) tests before and after training. We extracted DNA from the muscle biopsies and performed global methylation using Illumina's Methylation EPIC 850K BeadChip. Training significantly increased peak aerobic capacity and insulin-stimulated glucose disposal. Fasting serum insulin and insulin levels during the steady state of the clamp were significantly lower post-training. Insulin clearance rates during the clamp increased following the training. We identified 13 increased and 90 decreased differentially methylated cytosines (DMCs) in response to 8 weeks of training. Of the 13 increased DMCs, 2 were within the following genes, FSTL3, and RP11-624M8.1. Of the 90 decreased DMCs, 9 were within the genes CNGA1, FCGR2A, KIF21A, MEIS1, NT5DC1, OR4D1, PRPF4B, SLC26A7, and ZNF280C. Moreover, pathway analysis showed an enrichment in metabolic and actin-cytoskeleton pathways for the decreased DMCs, and for the increased DMCs, an enrichment in signal-dependent regulation of myogenesis, NOTCH2 activation and transmission, and SMAD2/3: SMAD4 transcriptional activity pathways. Our findings showed that 8 weeks of exercise training alters skeletal muscle DNA methylation of specific genes and pathways in people with varying degrees of insulin sensitivity.
RESUMEN
Evidence suggests acetylation of human adenine nucleotide translocase 1 (ANT1) at lysine 23 (Lys23) reduces binding of ADP. Lys23 contributes to the positive charge that facilitates this interaction. This study was undertaken to characterize ANT1 abundance and acetylation by a novel method using small amounts of human skeletal muscle biopsies. Lysates of whole muscle or mitochondria from the same tissue were prepared from needle biopsies of vastus lateralis muscle of healthy volunteers. Lysed proteins were resolved on gels, the section containing ANT1 (surrounding 30 Kd) was excised, digested with trypsin, spiked with labeled unacetylated and acetylated synthetic standard peptides and analyzed by mass spectrometry. Natural logarithm transformation of data linearized ion intensities over a 10-fold range of peptide mass. Coefficients of variation ranged from 7 to 30% for ANT1 abundance and Lys23 acetylation. In three volunteers, ANT1 content was 8.36 ± 0.33 nmol/g wet weight muscle and 0.64 ± 0.05 nmol/mg mitochondria, so mitochondrial content was 13.3 ± 2.4 mg mitochondria per gram muscle. Acetylation of Lys23 averaged 14.3 ± 4.2% and 4.87 ± 1.84% in whole muscle and mitochondria, respectively. This assay makes it possible to assess effects of acetylation on the function of ANT1 in human muscle.
Asunto(s)
Translocador 1 del Nucleótido Adenina/metabolismo , Lisina/metabolismo , Músculo Esquelético/metabolismo , Acetilación , Translocador 1 del Nucleótido Adenina/análisis , Voluntarios Sanos , Humanos , Lisina/química , Músculo Esquelético/químicaRESUMEN
PURPOSE: Insulin resistant muscle is resistant to gene expression changes induced by acute exercise. This study was undertaken to identify transcription factors that differentially respond to exercise in insulin resistance. Candidate transcription factors were identified from analysis of 5'-untranslated regions (5'-UTRs) of exercise responsive genes and from analysis of the 5'-UTRs of genes coding for proteins that differ in abundance in insulin resistance. RESEARCH DESIGN AND METHODS: Twenty participants took part in this study. Insulin sensitivity was assessed by an euglycemic clamp. Participants were matched for aerobic capacity and performed a single 48 min bout of exercise with sets at 70 and 90% of maximum heart rate. Muscle biopsies were obtained at resting conditions, 30 min and 24 h after exercise. Global proteomics analysis identified differentially abundant proteins in muscle. The 5'-UTRs of genes coding for significant proteins were subjected to transcription factor enrichment analysis to identify candidate transcription factors. Q-rt-PCR to determine expression of candidate transcription factors was performed on RNA from resting and post-exercise muscle biopsies; immunoblots quantified protein abundance. RESULTS: Proteins involved in mitochondrial function, protein targeting and translation, and metabolism were among those significantly different between lean and obese groups. Transcription factor enrichment analysis of genes coding for these proteins revealed new candidate transcription factors to be evaluated along the previously identified factors. Q-rt-PCR analysis of RNA and immunoblot analysis from pre- and post-exercise muscle biopsies revealed several transcription and growth factors that had altered responses to exercise in insulin resistant participants. A significant increase (EGR3 and CTGF) and decrease (RELA and ATF2) in the mRNA expression of transcription and growth factors was found after exercise in the lean group, but not in the obese participants. CONCLUSIONS: These results confirm findings of an association between insulin sensitivity and transcription factor mRNA response to exercise and show that obesity also may be a sufficient prerequisite for exercise resistance. Analysis of the muscle proteome together with determination of effects of exercise on expression of transcription factors suggests that abnormal responses of transcription factors to exercise may be responsible for differences in protein abundances in insulin resistant muscle.
RESUMEN
VWA8 (Von Willebrand A Domain Containing Protein 8) is a AAA+ ATPase that is localized to the mitochondrial matrix and is widely expressed in highly energetic tissues. Originally found to be higher in abundance in livers of mice fed a high fat diet, deletion of the VWA8 gene in differentiated mouse AML12 hepatocytes unexpectedly produced a phenotype of higher mitochondrial and nonmitochondrial oxidative metabolism, higher ROS (reactive oxygen species) production mainly from NADPH oxidases, and increased HNF4a expression. The purposes of this study were first, to determine whether higher mitochondrial oxidative capacity in VWA8 null hepatocytes is the product of higher capacity in all aspects of the electron transport chain and oxidative phosphorylation, and second, the density of cristae in mitochondria and mitochondrial content was measured to determine if higher mitochondrial oxidative capacity is accompanied by greater cristae area and mitochondrial abundance. Electron transport chain complexes I, II, III, and IV activities all were higher in hepatocytes in which the VWA8 gene had been deleted using CRISPR/Cas9. A comparison of abundance of proteins in electron transport chain complexes I, III and ATP synthase previously determined using an unbiased proteomics approach in hepatocytes in which VWA8 had been deleted showed agreement with the activity assays. Mitochondrial cristae, the site where electron transport chain complexes are located, were quantified using electron microscopy and stereology. Cristae density, per mitochondrial area, was almost two-fold higher in the VWA8 null cells (P < 0.01), and mitochondrial area was two-fold higher in the VWA8 null cells (P < 0.05). The results of this study allow us to conclude that despite sustained, higher ROS production in VWA8 null cells, a global mitochondrial compensatory response was maintained, resulting in overall higher mitochondrial oxidative capacity.
RESUMEN
During intercellular communication, cells release extracellular vesicles such as exosomes, which contain proteins, ncRNAs and mRNAs that can influence proliferation and/or trigger apoptosis in recipient cells, and have been proposed to play an essential role in promoting invasion of tumor cells and in the preparation of metastatic niches. Our group proposed the antisense non-coding mitochondrial RNA (ASncmtRNA) as a new target for cancer therapy. ASncmtRNA knockdown using an antisense oligonucleotide (ASO-1537S) causes massive death of tumor cells but not normal cells and strongly reduces metastasis in mice. In this work, we report that exosomes derived from ASO-1537S-treated MDA-MB-231 breast cancer cells (Exo-1537S) inhibits tumorigenesis of recipient cells, in contrast to exosomes derived from control-ASO-treated cells (Exo-C) which, in contrast, enhance these properties. Furthermore, an in vivo murine peritoneal carcinomatosis model showed that Exo-1537S injection reduced tumorigenicity compared to controls. Proteomic analysis revealed the presence of Lactadherin and VE-Cadherin in exosomes derived from untreated cells (Exo-WT) and Exo-C but not in Exo-1537S, and the latter displayed enrichment of proteasomal subunits. These results suggest a role for these proteins in modulation of tumorigenic properties of exosome-recipient cells. Our results shed light on the mechanisms through which ASncmtRNA knockdown affects the preparation of breast cancer metastatic niches in a peritoneal carcinomatosis model.
Asunto(s)
Exosomas/metabolismo , Mitocondrias/genética , ARN no Traducido/metabolismo , Animales , Antígenos CD/metabolismo , Antígenos de Superficie/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Cadherinas/metabolismo , Carcinogénesis/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Humanos , Ratones , Proteínas de la Leche/metabolismo , Oligorribonucleótidos Antisentido/metabolismo , Oligorribonucleótidos Antisentido/farmacología , ARN no Traducido/antagonistas & inhibidores , ARN no Traducido/genética , Trasplante HeterólogoRESUMEN
Breast cancer is one of the most frequently diagnosed cancers and the leading cause of cancer-related deaths in women worldwide, whereby mortality is largely attributable to the development of distant metastasis. Caveolin-1 (CAV1) is a multifunctional membrane protein that is typically upregulated in the final stages of cancer and promotes migration and invasion of tumor cells. Elevated levels of CAV1 have been detected in extracellular vesicles (EVs) from advanced cancer patients. EVs are lipid enclosed vesicular structures that contain bioactive proteins, DNA and RNAs, which can be transferred to other cells and promote metastasis. Therefore, we hypothesized that CAV1 containing EVs released from breast cancer cells may enhance migration and invasion of recipient cells. EVs were purified from conditioned media of MDA-MB-231 wild-type (WT), MDA-MB-231 (shCAV1; possessing the plasmid pLKO.1 encoding a 'small hairpin' directed against CAV1) and MDA-MB-231 (shC) short hairpin control cells. Nanoparticle tracking analysis revealed an average particle size of 40-350 nm for all preparations. As anticipated, CAV1 was detected in MDA-MB-231 WT and shC EVs, but not in MDA-MB-231 (shCAV1) EVs. Mass spectrometry analysis revealed the presence of specific cell adhesion-related proteins, such as Cyr61, tenascin (TNC) and S100A9 only in WT and shC, but not in shCAV1 EVs. Importantly, EVs containing CAV1 promoted migration and invasion of cells lacking CAV1. We conclude that the presence of CAV1 in EVs from metastatic breast cancer cells is associated with enhanced migration and invasiveness of recipient cells in vitro, suggesting that intercellular communication promoted by EVs containing CAV1 will likely favor metastasis in vivo.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Caveolina 1/genética , Adhesión Celular/efectos de los fármacos , Neoplasias de la Mama/química , Neoplasias de la Mama/patología , Caveolina 1/química , Comunicación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Vesículas Extracelulares/química , Femenino , Humanos , Células MCF-7 , Metástasis de la NeoplasiaRESUMEN
The VWA8 gene was first identified by the Kazusa cDNA project and named KIAA0564. Based on the observation, by similarity, that the protein encoded by KIAA0564 contains a Von Willebrand Factor 8 domain, KIAA0564 was named Von Willebrand Domain-containing Protein 8 (VWA8). The function of VWA8 protein is almost unknown. The purpose of this study was to characterize the tissue distribution, cellular location, and function of VWA8. In mice VWA8 protein was mostly distributed in liver, kidney, heart, pancreas and skeletal muscle, and is present as a long isoform and a shorter splice variant (VWA8a and VWA8b). VWA8 protein and mRNA were elevated in mouse liver in response to high fat feeding. Sequence analysis suggests that VWA8 has a mitochondrial targeting sequence and domains responsible for ATPase activity. VWA8 protein was targeted exclusively to mitochondria in mouse AML12 liver cells, and this was prevented by deletion of the targeting sequence. Moreover, the VWA8 short isoform overexpressed in insect cells using a baculovirus construct had in vitro ATPase activity. Deletion of the Walker A motif or Walker B motif in VWA8 mostly blocked ATPase activity, suggesting Walker A motif or Walker B motif are essential to the ATPase activity of VWA8. Finally, homology modeling suggested that VWA8 may have a structure most confidently similar to dynein motor proteins.
Asunto(s)
Adenosina Trifosfatasas/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Adenosina Trifosfatasas/química , Adenosina Trifosfatasas/genética , Animales , Células Cultivadas , Biología Computacional , Proteínas de la Matriz Extracelular/química , Proteínas de la Matriz Extracelular/genética , Perfilación de la Expresión Génica , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Ibervillea sonorae (S. Watson) Greene (Cucurbitaceae), a plant used for the empirical treatment of type 2 diabetes in México, exerts antidiabetic effects on animal models but its mechanism of action remains unknown. The aim of this study is to investigate the antidiabetic mechanism of an Ibervillea sonorae aqueous extract (ISE). MATERIALS AND METHODS: Non-toxic ISE concentrations were assayed on the glucose uptake by insulin-sensitive and insulin-resistant murine and human cultured adipocytes, both in the absence or the presence of insulin signaling pathway inhibitors, and on murine and human adipogenesis. Chemical composition of ISE was examined by spectrophotometric and HPLC techniques. RESULTS: ISE stimulated the 2-NBDGlucose uptake by mature adipocytes in a concentration-dependent manner. ISE 50 µg/ml induced the 2-NBDG uptake in insulin-sensitive 3T3-F442A, 3T3-L1 and human adipocytes by 100%, 63% and 33%, compared to insulin control. Inhibitors for the insulin receptor, PI3K, AKT and GLUT4 blocked the 2-NBDG uptake in murine cells, but human adipocytes were insensitive to the PI3K inhibitor Wortmannin. ISE 50 µg/ml also stimulated the 2-NBDG uptake in insulin-resistant adipocytes by 117% (3T3-F442A), 83% (3T3-L1) and 48% (human). ISE induced 3T3-F442A adipogenesis but lacked proadipogenic effects on 3T3-L1 and human preadipocytes. Chemical analyses showed the presence of phenolics in ISE, mainly an appreciable concentration of gallic acid. CONCLUSION: Ibervillea sonorae exerts its antidiabetic properties by means of hydrosoluble compounds stimulating the glucose uptake in human preadipocytes by a PI3K-independent pathway and without proadipogenic effects.
Asunto(s)
Adipocitos/efectos de los fármacos , Cucurbitaceae/química , Hipoglucemiantes/farmacología , Extractos Vegetales/farmacología , Células 3T3 , Adipocitos/metabolismo , Adipogénesis/efectos de los fármacos , Animales , Células Cultivadas , Cromatografía Líquida de Alta Presión , Relación Dosis-Respuesta a Droga , Glucosa/metabolismo , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/aislamiento & purificación , Insulina/metabolismo , Resistencia a la Insulina , Medicina Tradicional , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Transducción de Señal/efectos de los fármacos , EspectrofotometríaRESUMEN
Isoorientin (ISO) is a plant C-glycosylflavonoid with purported antidiabetic effects but unexplored mechanisms of action. To gain insight into its antidiabetic mechanisms, we assayed nontoxic ISO concentrations on the 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxy-d-glucose (2-NBDG) uptake by murine 3T3-F442A and human sc adipocytes. In insulin-sensitive adipocytes, ISO stimulated the 2-NBDG uptake by 210% (murine) and 67% (human), compared with insulin treatment. Notably, ISO also induced 2-NBDG uptake in murine (139%) and human (60%) adipocytes made resistant to insulin by treatment with TNF-α, compared with the incorporation induced in these cells by rosiglitazone. ISO induction of glucose uptake in adipocytes was abolished by inhibitors of the insulin signaling pathway. These inhibitors also blocked the proper phosphorylation of insulin signaling pathway components induced by ISO in both insulin-sensitive and insulin-resistant adipocytes. Additionally, ISO stimulated the transcription of genes encoding components of insulin signaling pathway in murine insulin-sensitive and insulin-resistant adipocytes. In summary, we show here that ISO exerts its antidiabetic effects by activating the insulin signaling pathway in adipocytes, reverts the insulin resistance caused in these cells by TNF-α by stimulating the proper phosphorylation of proteins in this signaling pathway, and induces the expression of genes encoding these proteins.
Asunto(s)
Adipocitos/efectos de los fármacos , Resistencia a la Insulina/fisiología , Insulina/metabolismo , Luteolina/farmacología , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacología , 4-Cloro-7-nitrobenzofurazano/análogos & derivados , 4-Cloro-7-nitrobenzofurazano/farmacología , Adipocitos/metabolismo , Animales , Línea Celular , Desoxiglucosa/análogos & derivados , Desoxiglucosa/farmacología , Transportador de Glucosa de Tipo 4/genética , Transportador de Glucosa de Tipo 4/metabolismo , Humanos , Insulina/genética , Proteínas Sustrato del Receptor de Insulina/genética , Proteínas Sustrato del Receptor de Insulina/metabolismo , Ratones , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Transducción de Señal/fisiologíaRESUMEN
ETHNOPHARMACOLOGICAL IMPORTANCE: Justicia spicigera is a plant species used for the Teenak (Huesteca Potosina) and Mayan (Yucatan peninsula) indigenous for the empirical treatment of diabetes, infections and as stimulant. AIM OF THE STUDY: To evaluate the cytotoxicity, antioxidant and antidiabetic properties of J. spicigera. MATERIALS AND METHODS: The effects of ethanolic extracts of J. spicigera (JSE) on the glucose uptake in insulin-sensitive and insulin-resistant murine 3T3-F442A and human subcutaneous adipocytes was evaluated. The antioxidant activities of the extract of JSE was determined by ABTS and DPPH methods. Additionally, it was evaluated the antidiabetic properties of JSE on T2DM model. RESULTS: JSE stimulated 2-NBDG uptake by insulin-sensitive and insulin-resistant human and murine adipocytes in a concentration-dependent manner with higher potency than rosiglitazone 1mM. JSE showed antioxidant effects in vitro and induced glucose lowering effects in normoglycemic and STZ-induced diabetic rats. CONCLUSION: The antidiabetic effects of administration of J. spicigera are related to the stimulation of glucose uptake in both insulin-sensitive and insulin-resistant murine and human adipocytes and this evidence justify its empirical use in Traditional Medicine. In addition, J. spicigera exerts glucose lowering effects in normoglycemic and STZ-induced diabetic rats.
Asunto(s)
Acanthaceae , Antioxidantes/uso terapéutico , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Fitoterapia , Extractos Vegetales/uso terapéutico , Células 3T3 , 4-Cloro-7-nitrobenzofurazano/análogos & derivados , 4-Cloro-7-nitrobenzofurazano/metabolismo , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Animales , Antioxidantes/farmacología , Benzotiazoles/metabolismo , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Desoxiglucosa/análogos & derivados , Desoxiglucosa/metabolismo , Diabetes Mellitus Experimental/metabolismo , Etanol/química , Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Humanos , Hipoglucemiantes/farmacología , Quempferoles/análisis , Masculino , Ratones , Extractos Vegetales/farmacología , Hojas de la Planta , Ratas , Ratas Wistar , Solventes/química , Ácidos Sulfónicos/metabolismoRESUMEN
Some Magnolia (Magnoliaceae) species are used for the empirical treatment of diabetes mellitus, but the antidiabetic properties of Magnolia dealbata have not yet been experimentally validated. Here we report that an ethanolic extract of Magnolia dealbata seeds (MDE) and its active principles honokiol (HK) and magnolol (MG) induced the concentration-dependent 2-NBDG uptake in murine 3T3-F442A and human subcutaneous adipocytes. In insulin-sensitive adipocytes, MDE 50 µg/ml induced the 2-NBDG uptake by 30% respect to insulin, while HK and MG, 30 µM each, did it by 50% (murine) and 40% (human). The simultaneous application of HK and MG stimulated 2-NBDG uptake by 70% in hormone-sensitive cells, on which Magnolia preparations exerted synergic effects with insulin. In insulin-resistant adipocytes, MDE, HK and MG induced 2-NBDG uptake by 57%, 80% and 96% respect to Rosiglitazone (RGZ), whereas HK and MG simultaneously applied stimulated 2-NBDG uptake more efficiently than RGZ (120%) in both murine and human adipocytes. Inhibitors of the insulin-signaling pathway abolished the glucose uptake induced by Magnolia dealbata preparations, suggesting that their antidiabetic effects are mediated by this signaling pathway. In addition, MDE, HK and MG exerted only mild to moderate proadipogenic effects on 3T3-F442A and human preadipocytes, although the combined application of HK and MG markedly increased the lipid accumulation in both cell types. In summary, Magnolia dealbata and its active principles HK and MG stimulate glucose uptake in insulin-sensitive and insulin-resistant murine and human adipocytes using the insulin signaling pathway.
Asunto(s)
Adipocitos/efectos de los fármacos , Compuestos de Bifenilo/farmacología , Glucosa/metabolismo , Lignanos/farmacología , Magnolia/química , Transducción de Señal , Células 3T3 , 4-Cloro-7-nitrobenzofurazano/análogos & derivados , 4-Cloro-7-nitrobenzofurazano/metabolismo , Adipogénesis , Animales , Supervivencia Celular/efectos de los fármacos , Desoxiglucosa/análogos & derivados , Desoxiglucosa/metabolismo , Sinergismo Farmacológico , Humanos , Hipoglucemiantes/farmacología , Insulina/metabolismo , Metabolismo de los Lípidos , Ratones , Extractos Vegetales/farmacologíaRESUMEN
The antimicrobial effects of the Mexican medicinal plants Guazuma ulmifolia, Justicia spicigera, Opuntia joconostle, O. leucotricha, Parkinsonia aculeata, Phoradendron longifolium, P. serotinum, Psittacanthus calyculatus, Tecoma stans and Teucrium cubense were tested against several human multi-drug resistant pathogens, including three Gram (+) and five Gram (-) bacterial species and three fungal species using the disk-diffusion assay. The cytotoxicity of plant extracts on human cancer cell lines and human normal non-cancerous cells was also evaluated using the MTT assay. Phoradendron longifolium, Teucrium cubense, Opuntia joconostle, Tecoma stans and Guazuma ulmifolia showed potent antimicrobial effects against at least one multidrug-resistant microorganism (inhibition zone > 15 mm). Only Justicia spicigera and Phoradendron serotinum extracts exerted active cytotoxic effects on human breast cancer cells (IC50 < or = 30 microg/mL). The results showed that Guazuma ulmifolia produced potent antimicrobial effects against Candida albicans and Acinetobacter lwoffii, whereas Justicia spicigera and Phoradendron serotinum exerted the highest toxic effects on MCF-7 and HeLa, respectively, which are human cancer cell lines. These three plant species may be important sources of antimicrobial and cytotoxic agents.
Asunto(s)
Antiinfecciosos/farmacología , Antineoplásicos Fitogénicos/farmacología , Extractos Vegetales/farmacología , Plantas Medicinales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , MéxicoRESUMEN
AIM OF THE STUDY: Tecoma stans (L.) Juss. ex Kunth (Bignoniaceae) and Teucrium cubense Jacq (Lamiaceae) are plants extensively used for the empirical treatment of diabetes mellitus, but their antidiabetic mechanisms remain to be clarified. In this study, the effect of aqueous extracts of Tecoma stans (TSE) and Teucrium cubense (TCE) on the glucose uptake in adipose cells was evaluated. MATERIALS AND METHODS: Non-toxic concentrations of TSE and TCE were assayed on the adipogenesis and 2-NBDglucose uptake in insulin-sensitive and insulin-resistant murine 3T3-F442A and human subcutaneous adipocytes. RESULTS: Both extracts stimulated 2-NBDG uptake by insulin-sensitive and insulin-resistant adipocytes in a concentration-dependent manner. In insulin-sensitive cells, TSE 70 microg/ml stimulated 2-NBDG uptake by 193% (murine) and by 115% (human), whereas the same concentration of TCE induced the 2-NBDG uptake by 112% (murine) and 54% (human). In insulin-resistant adipocytes, TSE induced the 2-NBDG uptake by 94% (murine) and 70% (human), compared with the incorporation shown by insulin-sensitive adipocytes stimulated by the hormone, whereas TCE induced the incorporation of 2-NBDG by 69% (murine) and 31% (human). On the other hand, TSE and TCE exerted only minimal or null proadipogenic effects on murine and human preadipocytes. CONCLUSION: Tecoma stans and Teucrium cubense exert their antidiabetic effects stimulating glucose uptake in both insulin-sensitive and insulin-resistant murine and human adipocytes without significant proadipogenic or antiadipogenic side effects.
Asunto(s)
Adipocitos/efectos de los fármacos , Bignoniaceae/química , Glucosa/metabolismo , Hipoglucemiantes/farmacología , Insulina/farmacología , Extractos Vegetales/farmacología , Teucrium/química , Células 3T3 , Adipocitos/metabolismo , Adipogénesis/efectos de los fármacos , Alcaloides/análisis , Animales , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Flavonoides/análisis , Glucosa/análogos & derivados , Humanos , Resistencia a la Insulina , Ratones , Fenoles/análisis , Fitoterapia , Componentes Aéreos de las Plantas/química , Extractos Vegetales/química , Plantas Medicinales/químicaRESUMEN
Eleven new oxides, derived from yttrium barium copper oxide by replacing the square-planar copper [Cu-O4] of the basal plane of the triple perovskite-based structure with octahedral Cr(IV), have been prepared at high pressure and temperature. Their crystal structures have been determined, and their complex microstructure has been established by means of high-resolution electron microscopy and electron diffraction. The materials have a general formula of CrSr2RECu2O8 (RE = La, Pr, Nd, Eu, Gd, Tb, Dy, Y, Ho, Er, and Lu); they are tetragonal, show the symmetry of space group P4/mmm, and do not appear to be superconducting.
RESUMEN
The temperature dependence of the crystal structure and electronic properties of brownmillerite-like Ca(2.5)Sr(0.5)GaMn(2)O(8) has been studied by neutron powder diffraction and muSR spectroscopy. The results show that short-range 2D magnetic order begins to develop within the perovskite-like bilayers of MnO(6) octahedra approximately 50 K above the 3D Néel temperature of approximately 150 K. The bilayers show a structural response to the onset of magnetism throughout this temperature range whereas the GaO(4) layers that separate the bilayers only respond below the 3D ordering temperature. XANES spectroscopy shows that the sample contains Mn(3+) and Mn(4+) cations in a 1:1 ratio, and the behavior in the region of the Néel transition is interpreted as a local charge ordering. Electron diffraction and high-resolution electron microscopy have been used to show that the local microstructure is more complex than the average structure revealed by neutron diffraction, and that microdomains exist in which the GaO(4) tetrahedra show different orientations. It is argued that the bonding requirements of diamagnetic gallium control the electronic behavior within the perovskite-like bilayers.