Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.257
Filtrar
1.
Nat Commun ; 12(1): 658, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33510169

RESUMO

A microneedle array is an attractive option for a minimally invasive means to break through the skin barrier for efficient transdermal drug delivery. Here, we report the applications of solid polymer-based ion-conductive porous microneedles (PMN) containing interconnected micropores for improving iontophoresis, which is a technique of enhancing transdermal molecular transport by a direct current through the skin. The PMN modified with a charged hydrogel brings three innovative advantages in iontophoresis at once: (1) lowering the transdermal resistance by low-invasive puncture of the highly resistive stratum corneum, (2) transporting of larger molecules through the interconnected micropores, and (3) generating electroosmotic flow (EOF). In particular, the PMN-generated EOF greatly enhances the transdermal molecular penetration or extraction, similarly to the flow induced by external pressure. The enhanced efficiencies of the EOF-assisted delivery of a model drug (dextran) and of the extraction of glucose are demonstrated using a pig skin sample. Furthermore, the powering of the PMN-based transdermal EOF system by a built-in enzymatic biobattery (fructose / O2 battery) is also demonstrated as a possible totally organic iontophoresis patch.


Assuntos
Sistemas de Liberação de Medicamentos/instrumentação , Sistemas de Liberação de Medicamentos/métodos , Epiderme/metabolismo , Pele/metabolismo , Administração Cutânea , Animais , Dextranos/administração & dosagem , Dextranos/metabolismo , Dextranos/farmacocinética , Eletro-Osmose , Fluoresceína-5-Isotiocianato/administração & dosagem , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/metabolismo , Fluoresceína-5-Isotiocianato/farmacocinética , Glucose/administração & dosagem , Glucose/metabolismo , Glucose/farmacocinética , Humanos , Iontoforese/instrumentação , Iontoforese/métodos , Masculino , Microinjeções , Agulhas , Padrões Moleculares Associados a Patógenos/administração & dosagem , Padrões Moleculares Associados a Patógenos/metabolismo , Padrões Moleculares Associados a Patógenos/farmacocinética , Porosidade , Suínos
2.
Am J Physiol Endocrinol Metab ; 320(3): E425-E437, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33356994

RESUMO

Aerobic exercise in type 1 diabetes (T1D) causes rapid increase in glucose utilization due to muscle work during exercise, followed by increased insulin sensitivity after exercise. Better understanding of these changes is necessary for models of exercise in T1D. Twenty-six individuals with T1D underwent three sessions at three insulin rates (100%, 150%, 300% of basal). After 3-h run-in, participants performed 45 min aerobic exercise (moderate or intense). We determined area under the curve for endogenous glucose production (AUCEGP) and rate of glucose disappearance (AUCRd) over 45 min from exercise start. A novel application of linear regression of Rd across the three insulin sessions allowed separation of insulin-mediated from non-insulin-mediated glucose uptake before, during, and after exercise. AUCRd increased 12.45 mmol/L (CI = 10.33-14.58, P < 0.001) and 13.13 mmol/L (CI = 11.01-15.26, P < 0.001) whereas AUCEGP increased 1.66 mmol/L (CI = 1.01-2.31, P < 0.001) and 3.46 mmol/L (CI = 2.81-4.11, P < 0.001) above baseline during moderate and intense exercise, respectively. AUCEGP increased during intense exercise by 2.14 mmol/L (CI = 0.91-3.37, P < 0.001) compared with moderate exercise. There was significant effect of insulin infusion rate on AUCRd equal to 0.06 mmol/L per % above basal rate (CI = 0.05-0.07, P < 0.001). Insulin-mediated glucose uptake rose during exercise and persisted hours afterward, whereas non-insulin-mediated effect was limited to the exercise period. To our knowledge, this method of isolating dynamic insulin- and non-insulin-mediated uptake has not been previously employed during exercise. These results will be useful in informing glucoregulatory models of T1D. The study has been registered at www.clinicaltrials.gov as NCT03090451.NEW & NOTEWORTHY Separating insulin and non-insulin glucose uptake dynamically during exercise in type 1 diabetes has not been done before. We use a multistep process, including a previously described linear regression method, over three insulin infusion sessions, to perform this separation and can graph these components before, during, and after exercise for the first time.


Assuntos
Diabetes Mellitus Tipo 1/metabolismo , Exercício Físico/fisiologia , Glucose/farmacocinética , Insulina/fisiologia , Adolescente , Adulto , Glicemia/metabolismo , Feminino , Humanos , Hiperinsulinismo/metabolismo , Hipoglicemia/metabolismo , Insulina/administração & dosagem , Insulina/metabolismo , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Esforço Físico/fisiologia , Adulto Jovem
3.
Food Chem ; 340: 127908, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32889206

RESUMO

This study aims to evaluate the effects of in vitro digestion of rice and common bean blends on phenolics content and profile. Black and carioca beans were used as common bean sources. Blends consisted of 25:75, 50:50, and 75:25 polished rice:beans (w/w). Pure rice or pure beans were also analyzed. Phenolic compounds were determined in raw, cooked, and digested samples. The glucose release through in vitro digestion was slower as the proportion of black beans or carioca beans increased. Starch digestibility ranged between 41.1 in 100% carioca bean to 84.4% in 100% rice. Hydroxybenzoic acid, ferulic acid, p-coumaric acid, catechin, and epicatechin were the most abundant phenolics detected in the studied samples. Considering the content of phenolic compounds determined in the raw, cooked, and digested grains, only a small fraction was available for absorption in the gut, with amounts varying from 0.1 to 0.6 µg·g-1.


Assuntos
Oryza/química , Phaseolus/química , Fenóis/análise , Amido/química , Amido/farmacocinética , Catequina/análise , Catequina/química , Culinária , Digestão , Glucose/farmacocinética , Hidroxibenzoatos/análise , Hidroxibenzoatos/química , Fenóis/química , Amido/análise
4.
Chem Biol Interact ; 330: 109198, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32692981

RESUMO

Quercetin 3-O-beta-d-glucopyranoside (isoquercetin) is one of the most frequent metabolites of the Passiflora ligularis Juss. The purpose of this study was to investigate the effect of the aqueous extract and ethanol fraction from P. ligularis Juss leaves on glycaemia and the mechanism of action of isoquercetin on glucose uptake. In the glucose tolerance test, the aqueous extract and ethanol fraction from P. ligularis Juss (125 mg/kg to 500 mg/kg o. g.) reduced glycaemia and increased the hepatic and muscular glycogen content. Phytochemical analysis evidenced the dominant presence of isoquercetin in the extract and fraction from leaves of P. ligularis Juss. Isoquercetin mediates the stimulatory effect on glucose uptake independent of insulin receptor activation but, involve PI3K, MAPK, MEK/ERK pathways and de novo protein synthesis to GLUT-4 translocation. Overall findings revealed that isoquercetin and aqueous extract and ethanol fraction of P. ligularis Juss leaves might be a promising functional food or medicine for the treatment or prevention of diabetes.


Assuntos
Glucose/farmacocinética , Músculo Esquelético/metabolismo , Passiflora/química , Quercetina/análogos & derivados , Animais , Transporte Biológico , Diabetes Mellitus/prevenção & controle , Transportador de Glucose Tipo 4/metabolismo , Compostos Fitoquímicos/análise , Extratos Vegetais/química , Folhas de Planta/química , Quercetina/isolamento & purificação , Quercetina/farmacologia , Ratos
5.
Phytomedicine ; 68: 153178, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32126492

RESUMO

BACKGROUND: Lowering blood glucose levels by increasing glucose uptake in insulin target tissues, such as skeletal muscle and adipose tissue, is one strategy to discover and develop antidiabetic drugs from natural products used as traditional medicines. PURPOSE: Our goal was to reveal the mechanism and activity of acacetin (5,7-dihydroxy-4'-methoxyflavone), one of the major compounds in Agastache rugose, in stimulating glucose uptake in muscle cells. METHODS: To determine whether acacetin promotes GLUT4-dependent glucose uptake in cultured L6 skeletal muscle cells, we performed a [14C] 2-deoxy-D-glucose (2-DG) uptake assay after treating differentiated L6-GLUT4myc cells with acacetin. RESULTS: Acacetin dose-dependently increased 2-DG uptake by enhancing GLUT4 translocation to the plasma membrane. Our results revealed that acacetin activated the CaMKII-AMPK pathway by increasing intracellular calcium concentrations. We also found that aPKCλ/ζ phosphorylation and intracellular reactive oxygen species (ROS) production were involved in acacetin-induced GLUT4 translocation. Moreover, acacetin-activated AMPK inhibited intracellular lipid accumulation and increased 2-DG uptake in HepG2 cells. CONCLUSION: Taken together, these results suggest that acacetin might be useful as an antidiabetic functional ingredient. Subsequent experiments using disease model animals are needed to verify our results.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Flavonas/farmacologia , Glucose/metabolismo , Insulina/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Animais , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Células Cultivadas , Desoxiglucose/farmacocinética , Relação Dose-Resposta a Droga , Glucose/farmacocinética , Transportador de Glucose Tipo 4/metabolismo , Células Hep G2 , Humanos , Hipoglicemiantes/farmacologia , Fibras Musculares Esqueléticas/metabolismo , Fosforilação , Transporte Proteico/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
6.
PLoS One ; 15(2): e0228602, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32027706

RESUMO

OBJECTIVE: The inflammatory activity of visceral adipose tissue (VAT) is elevated in metabolic syndrome (MS), and associated with vulnerability to atherosclerosis. Inflammation can be assessed by glucose uptake in atherosclerotic plaques. We investigated whether the glucose uptake of VAT, assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), is associated with systemic inflammatory status, and related to the number of MS components. METHODS: 18F-FDG PET/CT was performed in a total of 203 participants: 59 without MS component; M(0), 92 with one or two MS components; M(1-2), and 52 with MS. Glucose uptake in VAT was evaluated using the mean standardized uptake value (SUVmean) and the maximum SUV (SUVmax). Glucose uptakes of immune-related organs such as the spleen and bone marrow (BM) were evaluated using the SUVmax. RESULTS: VAT SUVmax correlated with high-sensitivity C-reactive protein (hsCRP) and the SUVmax of spleen and BM, which reflect the status of systemic inflammation. Both hsCRP and the SUVmax of the spleen and BM were higher in the MS group than in the M(1-2) or M(0) groups. In VAT, SUVmax increased with increasing number of MS components, while SUVmean decreased. CONCLUSIONS: The SUVmax and SUVmean of VAT assessed by 18F-FDG PET/CT reflected inflammation-driven unique glucose metabolism in the VAT of MS patients, distinct from that of atherosclerotic plaques.


Assuntos
Glucose/farmacocinética , Inflamação/diagnóstico por imagem , Gordura Intra-Abdominal/metabolismo , Síndrome Metabólica/patologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Idoso , Medula Óssea/metabolismo , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/metabolismo , Baço/metabolismo
7.
Metabolism ; 103: 154030, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31778707

RESUMO

BACKGROUND: Exogenous carbohydrate oxidation is lower during steady-state aerobic exercise in native lowlanders sojourning at high altitude (HA) compared to sea level (SL). However, the underlying mechanism contributing to reduction in exogenous carbohydrate oxidation during steady-state aerobic exercise performed at HA has not been explored. OBJECTIVE: To determine if alterations in glucose rate of appearance (Ra), disappearance (Rd) and metabolic clearance rate (MCR) at HA provide a mechanism for explaining the observation of lower exogenous carbohydrate oxidation compared to during metabolically-matched, steady-state exercise at SL. METHODS: Using a randomized, crossover design, native lowlanders (n = 8 males, mean ±â€¯SD, age: 23 ±â€¯2 yr, body mass: 87 ±â€¯10 kg, and VO2peak: SL 4.3 ±â€¯0.2 L/min and HA 2.9 ±â€¯0.2 L/min) consumed 145 g (1.8 g/min) of glucose while performing 80-min of metabolically-matched (SL: 1.66 ±â€¯0.14 V̇O2 L/min 329 ±â€¯28 kcal, HA: 1.59 ±â€¯0.10 V̇O2 L/min, 320 ±â€¯19 kcal) treadmill exercise in SL (757 mmHg) and HA (460 mmHg) conditions after a 5-h exposure. Substrate oxidation rates (g/min) and glucose turnover (mg/kg/min) during exercise were determined using indirect calorimetry and dual tracer technique (13C-glucose oral ingestion and [6,6-2H2]-glucose primed, continuous infusion). RESULTS: Total carbohydrate oxidation was higher (P < 0.05) at HA (2.15 ±â€¯0.32) compared to SL (1.39 ±â€¯0.14). Exogenous glucose oxidation rate was lower (P < 0.05) at HA (0.35 ±â€¯0.07) than SL (0.44 ±â€¯0.05). Muscle glycogen oxidation was higher at HA (1.67 ±â€¯0.26) compared to SL (0.83 ±â€¯0.13). Total glucose Ra was lower (P < 0.05) at HA (12.3 ±â€¯1.5) compared to SL (13.8 ±â€¯2.0). Exogenous glucose Ra was lower (P < 0.05) at HA (8.9 ±â€¯1.3) compared to SL (10.9 ±â€¯2.2). Glucose Rd was lower (P < 0.05) at HA (12.7 ±â€¯1.7) compared to SL (14.3 ±â€¯2.0). MCR was lower (P < 0.05) at HA (9.0 ±â€¯1.8) compared to SL (12.1 ±â€¯2.3). Circulating glucose and insulin concentrations were higher in response carbohydrate intake during exercise at HA compared to SL. CONCLUSION: Novel results from this investigation suggest that reductions in exogenous carbohydrate oxidation at HA may be multifactorial; however, the apparent insensitivity of peripheral tissue to glucose uptake may be a primary determinate.


Assuntos
Metabolismo dos Carboidratos , Exercício Físico/fisiologia , Glucose/farmacocinética , Hipóxia/metabolismo , Doença Aguda , Adolescente , Adulto , Metabolismo dos Carboidratos/efeitos dos fármacos , Estudos Cross-Over , Teste de Esforço , Humanos , Hipóxia/patologia , Masculino , Taxa de Depuração Metabólica , Oxirredução/efeitos dos fármacos , Consumo de Oxigênio/fisiologia , Adulto Jovem
8.
Nat Prod Res ; 34(9): 1238-1245, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-30663382

RESUMO

Dasiphora fruticosa L. (Rosaceae), also known as Potentilla fruticosa L. (syn.), is a hardy deciduous shrub widely distributed in the north temperate regions of the world. Three methylene bisflavan-3-ols (1-3), together with a procyanidin dimer, (-)-afzelechin-(4α→8)-(-)-afzelechin (4) were isolated for the first time from the branches and leaves of the titled plant, in addition to 11 known compounds (5-15). Their structures were elucidated by means of extensive spectroscopic analysis and by comparison with data reported in the literatures. Methylene 6,8-bis(7-O-glucosyl) catechin (1) was determined to be a new dimeric flavan-3-ol glycoside through a methylene linkage between C-8 and C-8 of two units. At a concentration of 128 µg/mL, the known compounds 9 - 13 exhibited antibacterial activities on Escherichia coli, Staphylococcus aureus subsp. aureus, Salmonella enterica subsp. enterica, and Pseudomonas aeruginosa. Compound 12 also showed certain glucose uptake stimulating activity.


Assuntos
Antibacterianos/isolamento & purificação , Flavonoides/isolamento & purificação , Potentilla/química , Rosaceae/química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Biflavonoides/isolamento & purificação , Catequina/isolamento & purificação , Glucose/farmacocinética , Glicosídeos/análise , Glicosídeos/isolamento & purificação , Fenóis/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Proantocianidinas/isolamento & purificação
9.
J Cereb Blood Flow Metab ; 40(3): 678-691, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-30890077

RESUMO

Triheptanoin is anticonvulsant in several seizure models. Here, we investigated changes in glucose metabolism by triheptanoin interictally in the chronic stage of the pilocarpine mouse epilepsy model. After injection of [U-13C6]-glucose (i.p.), enrichments of 13C in intermediates of glycolysis and the tricarboxylic acid (TCA) cycle were quantified in hippocampal extracts and maximal activities of enzymes in each pathway were measured. The enrichment of 13C glucose in plasma was similar across all groups. Despite this, we observed reductions in incorporation of 13C in several glycolytic intermediates compared to control mice suggesting glucose utilization may be impaired and/or glycogenolysis increased in the untreated interictal hippocampus. Triheptanoin prevented the interictal reductions of 13C incorporation in most glycolytic intermediates, suggesting it increased glucose utilization or - as an additional astrocytic fuel - it decreased glycogen breakdown. In the TCA cycle metabolites, the incorporation of 13C was reduced in the interictal state. Triheptanoin restored the correlation between 13C enrichments of pyruvate relative to most of the TCA cycle intermediates in "epileptic" mice. Triheptanoin also prevented the reductions of hippocampal pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase activities. Decreased glycogen breakdown and increased glucose utilization and metabolism via the TCA cycle in epileptogenic brain areas may contribute to triheptanoin's anticonvulsant effects.


Assuntos
Ciclo do Ácido Cítrico/efeitos dos fármacos , Epilepsia/metabolismo , Glucose , Glicólise/efeitos dos fármacos , Hipocampo/metabolismo , Complexo Cetoglutarato Desidrogenase/metabolismo , Piruvato Descarboxilase/metabolismo , Triglicerídeos/farmacologia , Animais , Doença Crônica , Modelos Animais de Doenças , Epilepsia/patologia , Glucose/análogos & derivados , Glucose/farmacocinética , Glucose/farmacologia , Hipocampo/patologia , Masculino , Camundongos
10.
Biol Trace Elem Res ; 193(2): 377-389, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31066020

RESUMO

Colon cancer in men and breast cancer in women are regarded as major health burdens, accounting for majority of cancer diagnoses globally. Doxorubicin (DOX) resistance in breast and colon cancers represents the main reason of unsuccessful therapy. The rationale of this study is to explore whether selenium nanoparticles (nano-Se) can overcome this resistance obstacle of DOX nanoparticles (nano-DOX) in these cancerous cells. Nano-Se and nano-DOX were manufactured and characterized using electron microscopy and Malvern ZetaSizer, applied separately or in the form of combinatorial regimen against human breast cancer cells (MCF7 and MDA-MB-231) and human colorectal cancer cells (HCT 116 and Caco-2). Cytotoxicity, early/late apoptosis, necrosis, cellular zinc, glucose uptake, and redox status were assessed after applying different nano-treatments versus their free counterparts. Nano-DOX induces cytotoxicity in MCF7 and Caco-2 more than MDA-MB-231 and HCT 116 cancerous cells. In addition, nano-DOX plus nano-Se diminish MCF7 and Caco-2 chemoresistance higher than MDA-MB-231 and HCT 116 cancerous cells. Moreover, Se and DOX nano-platforms inhibit glucose uptake. Furthermore, nano-DOX increases nitric oxide (NO) and malondialdehyde (MDA) in cancer cells' media, while nano-DOX combination with nano-Se rebalances the redox status with zinc augmentation. We reported that Caco-2 cancer cells are more sensitive than HCT 116 cancer cells to nano-DOX and nano-Se. Nano-DOX plus nano-Se induces cytotoxicity-mediated late apoptosis in Caco-2 more than HCT 116 cell lines. This de novo strategy could have great power to overcome the problem of DOX resistance during colon cancer therapy.


Assuntos
Apoptose/efeitos dos fármacos , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Nanopartículas/química , Selênio/farmacologia , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Transporte Biológico/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Células CACO-2 , Linhagem Celular Tumoral , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Doxorrubicina/química , Feminino , Glucose/metabolismo , Glucose/farmacocinética , Células HCT116 , Humanos , Células MCF-7 , Microscopia Eletrônica , Nanopartículas/ultraestrutura , Selênio/química
11.
Cancer Biomark ; 27(2): 189-194, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31796665

RESUMO

BACKGROUND: Ovarian clear cell carcinoma (CCC) is enriched in genes associated with glucose metabolism. OBJECTIVE: To evaluate the 18F-FDG PET/CT-based metabolic variables and the correlations with clinicopathologic features in OCCC patients. METHODS: We measured quantitative parameters including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). RESULTS: A total of 22 patients were included. PET/CT-based metabolic parameters were calculated for 20 patients because two had low glucose-uptake tumor. The median SUVmax was 7.25 (range 2.50-14.80). Spearman's correlation test revealed that the level of pre-operative serum cancer antigen 125 (CA 125) correlated significantly with MTV (P= 0.020) and TLG (P= 0.023). Interestingly, platinum-sensitive patients tended to have higher MTV/TLG though significance not achieved. On univariate analysis, the following four variables (stage, residual disease, platinum sensitivity and MTV50) were significant for both progression-free survival and overall survival. Besides, four metabolic parameters (MTV40, TLG40, TLG50 and TLG60) were significantly associated with patients' overall survival. Out of expectation, ovarian CCC patients with higher level of MTV/TLG tended to have better survival. CONCLUSIONS: 18F-FDG PET/CT-based metabolic volumetric parameters might be predicators for survival in ovarian CCC patients. Cautions should be taken when interpreting the results due to the small sample size.


Assuntos
Adenocarcinoma de Células Claras/diagnóstico por imagem , Adenocarcinoma de Células Claras/metabolismo , Fluordesoxiglucose F18 , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Glucose/metabolismo , Glucose/farmacocinética , Glicólise , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Taxa de Sobrevida , Carga Tumoral
12.
Nat Prod Res ; 34(13): 1827-1835, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30676074

RESUMO

Three new phenylacetamide glycosides (1-3) together with one known phenylacetamide glycoside (4) and two known flavonoid glycosides (5-6) were isolated from whole plants of Dracocephalum tanguticum. The structure of all compounds were elucidated based on spectroscopic data analysis and comparison with data reported in related literature. Compounds (1-3) were evaluated for their anti-hyperglycemic and anti-fungal (Candida albicans) activities, the results revealed that all of them showed moderate activity with 3T3-L1 adipocytes glucose consumption rate of 20.80 ± 1.47%, 21.48 ± 2.44%, and 21.57 ± 1.35%, respectively at the final concentration of 25 µM. However, none of them showed obvious Candida albicans inhibitory activity.


Assuntos
Antifúngicos/isolamento & purificação , Glicosídeos/farmacologia , Hipoglicemiantes/isolamento & purificação , Lamiaceae/química , Animais , Antifúngicos/química , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Linhagem Celular , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Glucose/farmacocinética , Glicosídeos/química , Glicosídeos/isolamento & purificação , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Camundongos , Estrutura Molecular , Análise Espectral
13.
Anal Chem ; 91(23): 15032-15039, 2019 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31694368

RESUMO

Detecting the effects of low oxygen on cell function is often dependent on monitoring the expression of a number of hypoxia markers. The time dependence of the appearance and stability of these markers varies between cell lines. Assessing cellular marker dynamics is also critical to determining how quickly cells respond to transient changes in oxygen levels that occurs with cycling hypoxia. We fabricated a manifold designed to use flow-encoding to produce sequential changes in gas mixtures delivered to a permeable-bottom 96-well plate. We show how this manifold and plate design can be used to expose cells to either static or cycling hypoxic conditions for eight different time periods thereby facilitating the study of the time-response of cells to altered oxygen environments. Using this device, we monitored the time-dependence of molecular changes in human PANC-1 pancreatic carcinoma and Caco-2 colon adenocarcinoma cells exposed to increasing periods of static or cycling hypoxia. Using immunohistochemistry, both cell lines show detectable levels of the marker protein hypoxia-inducible factor-1α (HIF-1α) after 3 h of exposure to static hypoxia. Cycling hypoxia increased the expression level of HIF-1α compared to static hypoxia. Both static and cycling hypoxia also increased glucose uptake and aldehyde dehydrogenase activity. This new device offers a facile screening approach to determine the kinetics of cellular alterations under varying oxygen conditions.


Assuntos
Hipóxia Celular , Oxigênio/metabolismo , Aldeído Desidrogenase/metabolismo , Células CACO-2 , Linhagem Celular Tumoral , Glucose/farmacocinética , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Oxigênio/farmacologia , Neoplasias Pancreáticas/patologia , Fatores de Tempo
14.
Cells ; 8(10)2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31547005

RESUMO

In cancers, tumor cells are exposed to fluctuating nutrient microenvironments with limiting supplies of glucose and glutamine. While the metabolic program has been related to the expression of oncogenes, only fractional information is available on how variable precarious nutrient concentrations modulate the cellular levels of metabolites and their metabolic pathways. We thus sought to obtain an overview of the metabolic routes taken by 13C-glucose-derived metabolites in breast cancer MCF-7 cells growing in combinations of limiting glucose and glutamine concentrations. Isotopologue profiles of key metabolites were obtained by gas chromatography/mass spectrometry (GC/MS). They revealed that in limiting and standard saturating medium conditions, the same metabolic routes were engaged, including glycolysis, gluconeogenesis, as well as the TCA cycle with glutamine and pyruvate anaplerosis. However, the cellular levels of 13C-metabolites, for example, serine, alanine, glutamate, malate, and aspartate, were highly sensitive to the available concentrations and the ratios of glucose and glutamine. Notably, intracellular lactate concentrations did not reflect the Warburg effect. Also, isotopologue profiles of 13C-serine as well as 13C-alanine show that the same glucose-derived metabolites are involved in gluconeogenesis and pyruvate replenishment. Thus, anaplerosis and the bidirectional flow of central metabolic pathways ensure metabolic plasticity for adjusting to precarious nutrient conditions.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Isótopos de Carbono/farmacocinética , Glucose/farmacocinética , Glutamina/farmacologia , Ciclo do Ácido Cítrico/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Glucose/farmacologia , Ácido Glutâmico/metabolismo , Glicólise/efeitos dos fármacos , Humanos , Ácido Láctico/metabolismo , Células MCF-7 , Malatos/metabolismo , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/fisiologia , Ácido Pirúvico/metabolismo , Microambiente Tumoral/efeitos dos fármacos
15.
Br J Radiol ; 92(1102): 20181051, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31322913

RESUMO

OBJECTIVE: To determine whether the apparent diffusion coefficient (ADC) on 3T MR imaging including diffusion-weighted MR imaging (DWI) correlate with the standardized uptake value (SUV) on 18F-FDG PET/CT in musculoskeletal tumours. METHODS: This retrospective cohort study included 57 patients (36 males, 21 females, mean age 54 years, range 12-90 years) with pathologically confirmed soft tissue (n = 32) and bone (n = 25) tumours who underwent 3T MR imaging including DWI and whole-body 18F-FDG PET/CT before treatment. 14 patients had follow-up MR imaging and 18F-FDG PET/CT after treatment. The minimum (ADCmin) and mean (ADCmean) ADCs of musculoskeletal tumour, ADC of normal skeletal muscle (ADCmus), SUVmax and SUVmean of musculoskeletal tumour were obtained. Correlation between ADCs and SUVs was assessed using Pearson correlation coefficients (r). ADCmin and SUVmax were compared between pretreatment and posttreatment by t-test. RESULTS: There was inverse correlation between SUVmax and the ratio ADCmin/ADCmus (r = - 0.505 to - 0.495, p ≤ 0.001) and between SUVmean and the ratio ADCmean/ADCmus (r = - 0.501 to - 0.493, p = 0.001). After treatment ADC was significantly increased whereas SUV was significantly decreased (p = 0.001). There was significant correlation in percent change between the initial and follow-up values of ADCmin and SUVmax (r = 0.750 to 0.773, p ≤ 0.005). The ADCmin was increased by 163% and SUVmax was decreased by 61% in 11 patients with treatment response. CONCLUSION: ADC at 3T MR DWI and SUV at 18F-FDG PET/CT have an inverse correlation in musculoskeletal tumours. ADVANCES IN KNOWLEDGE: Our study showed that ADC at 3T DWI and SUV at 18F-FDG PET/CT had an inverse correlation in musculoskeletal tumours.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/metabolismo , Imagem de Difusão por Ressonância Magnética/métodos , Fluordesoxiglucose F18/metabolismo , Neoplasias Musculares/diagnóstico por imagem , Neoplasias Musculares/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/patologia , Criança , Feminino , Glucose/farmacocinética , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/patologia , Variações Dependentes do Observador , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
16.
Am J Physiol Endocrinol Metab ; 317(3): E483-E493, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31265327

RESUMO

While the triple tracer isotope dilution method has enabled accurate estimation of carbohydrate turnover after a mixed meal, use of the simple carbohydrate glucose as the carbohydrate source limits its translational applicability to everyday meals that typically contain complex carbohydrates. Hence, utilizing the natural enrichment of [13C]polysaccharide in commercially available grains, we devised a novel tracer method to measure postprandial complex carbohydrate turnover and indices of insulin action and ß-cell function and compared the parameters to those obtained after a simple carbohydrate containing mixed meal. We studied healthy volunteers after either rice (n = 8) or sorghum (n = 8) and glucose (n = 16) containing mixed meals and modified the triple tracer technique to calculate carbohydrate turnover. All meals were matched for calories and macronutrient composition. Rates of meal glucose appearance (2,658 ± 736 vs. 4,487 ± 909 µM·kg-1·2 h-1), endogenous glucose production (-835 ± 283 vs. -1,123 ± 323 µM·kg-1·2 h-1) and glucose disappearance (1,829 ± 807 vs. 3,606 ± 839 µM·kg-1·2 h-1) differed (P < 0.01) between complex and simple carbohydrate containing meals, respectively. Interestingly, there were significant increase in indices of insulin sensitivity (32.5 ± 3.5 vs. 25.6 ± 3.2 10-5 (dl·kg-1·min-2)/pM, P = 0.006) and ß-cell responsivity (disposition index: 1,817 ± 234 vs. 1,236 ± 159 10-14 (dl·kg-1·min-2)/pM, P < 0.005) with complex than simple carbohydrate meals. We present a novel triple tracer approach to estimate postprandial turnover of complex carbohydrate containing mixed meals. We also report higher insulin sensitivity and ß-cell responsivity with complex than with simple carbohydrates in mixed meals of identical calorie and macronutrient compositions in healthy adults.


Assuntos
Metabolismo dos Carboidratos/fisiologia , Carboidratos da Dieta/metabolismo , Polissacarídeos , Compostos Radiofarmacêuticos , Adulto , Algoritmos , Isótopos de Carbono , Feminino , Glucose/metabolismo , Glucose/farmacocinética , Voluntários Saudáveis , Humanos , Resistência à Insulina , Células Secretoras de Insulina/metabolismo , Masculino , Refeições , Oryza , Período Pós-Prandial , Sorghum , Adulto Jovem
17.
PLoS One ; 14(7): e0217712, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31306426

RESUMO

Glycoconjugation to target the Warburg effect provides the potential to enhance selective uptake of anticancer or imaging agents by cancer cells. A Warburg effect targeting group, rationally designed to facilitate uptake by glucose transporters and promote cellular accumulation due to phosphorylation by hexokinase (HK), has been synthesised. This targeting group, the C2 modified glucose analogue 2-(2-[2-(2-aminoethoxy)ethoxy]ethoxy)-D-glucose, has been conjugated to the fluorophore nitrobenzoxadiazole to evaluate its effect on uptake and accumulation in cancer cells. The targeting vector has demonstrated inhibition of glucose phosphorylation by HK, indicating its interaction with the enzyme and thereby confirming the potential to facilitate an intracellular trapping mechanism for compounds it is conjugated with. The cellular uptake of the fluorescent analogue is dependent on the glucose concentration and is so to a greater extent than is that of the widely used fluorescent glucose analogue, 2-NBDG. It also demonstrates selective uptake in the hypoxic regions of 3D spheroid tumour models whereas 2-NBDG is distributed primarily through the normoxic regions of the spheroid. The increased selectivity is consistent with the blocking of alternative uptake pathways.


Assuntos
4-Cloro-7-nitrobenzofurazano/análogos & derivados , Desoxiglucose/análogos & derivados , Sistemas de Liberação de Medicamentos , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Glucose , Hexoquinase/metabolismo , Modelos Biológicos , Proteínas de Neoplasias/metabolismo , Neoplasias , 4-Cloro-7-nitrobenzofurazano/farmacocinética , 4-Cloro-7-nitrobenzofurazano/farmacologia , Hipóxia Celular , Linhagem Celular Tumoral , Desoxiglucose/farmacocinética , Desoxiglucose/farmacologia , Glucose/farmacocinética , Glucose/farmacologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia
18.
Planta Med ; 85(9-10): 729-737, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31167298

RESUMO

Rotundic acid and pedunculoside are the most abundant constituents in Ilicis Rotundae Cortex, and possess lipid-lowering activity. In this study, we evaluated the pharmacokinetic interactions of rotundic acid with pedunculoside and other ingredients from Ilicis Rotundae Cortex with rotundic acid and pedunculoside, and preliminarily investigated the effects of gut microbiota on their pharmacokinetics using a pseudo-germ-free rat model. After a single oral administration of each monomer, a monomer mixture, and Ilicis Rotundae Cortex extract to the conventional and pseudo-germ-free rats, rotundic acid and pedunculoside were quantified in plasma by an UPLC/Q-TOF-MS/MS method. The systemic exposure (maximum plasma concentration and area under concentration-time curve) of two analytes in conventional rats were increased in an approximately dose-dependent manner. Oral administration of rotundic acid and pedunculoside in the forms of a monomer mixture and Ilicis Rotundae Cortex extract to the conventional rats significantly decreased the systemic exposure compared with the monomer groups, which demonstrated the existence of significant pharmacokinetic interactions. The pseudo-germ-free rats were prepared by nonabsorbable antibiotic treatment, and the systemic exposure of two analytes were significantly decreased and most of the "time to reach the maximum" values were delayed in comparison to conventional rats, therefore gut microbiota might serve as an efficient absorption promoter. These results provide a scientific basis for the clinical application of the two bioactive constituents and Ilicis Rotundae Cortex.


Assuntos
Microbioma Gastrointestinal/fisiologia , Glucose/análogos & derivados , Triterpenos/farmacocinética , Administração Oral , Animais , Calibragem , Cromatografia Líquida/métodos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacocinética , Microbioma Gastrointestinal/efeitos dos fármacos , Glucose/administração & dosagem , Glucose/farmacocinética , Interações Ervas-Drogas , Masculino , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem/métodos , Triterpenos/administração & dosagem
19.
IET Nanobiotechnol ; 13(2): 226-229, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31051455

RESUMO

Diabetes mellitus has been considered as a heterogeneous metabolic disorder characterised by complete or relative impairment in the production of insulin by pancreatic ß-cells or insulin resistance. In the present study, propanoic acid, an active biocomponent isolated from Cassia auriculata is employed for the synthesis of propanoic acid functionalised gold nanoparticles (Pa@AuNPs) and its anti-diabetic activity has been demonstrated in vitro. In vitro cytotoxicity of synthesised Pa@AuNPs was performed in L6 myotubes. The mode of action of Pa@AuNPs exhibiting anti-diabetic potential was validated by glucose uptake assay in the presence of Genistein (insulin receptor tyrosine kinase inhibitor) and Wortmannin (Phosphatidyl inositide kinase inhibitor). Pa@AuNPs exhibited significant glucose uptake in L6 myotubes with maximum uptake at 50 ng/ml. Assays were performed to study the potential of Pa@AuNPs in the inhibition of protein-tyrosine phosphatase 1B, α-glucosidases, and α-amylase activity.


Assuntos
Glucose/metabolismo , Glucose/farmacocinética , Ouro/farmacologia , Hipoglicemiantes/farmacologia , Nanopartículas Metálicas/química , Nanocompostos/química , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ouro/química , Ouro/metabolismo , Hipoglicemiantes/química , Hipoglicemiantes/metabolismo , Ratos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...