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1.
Pharmaceuticals (Basel) ; 16(1)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36678614

RESUMO

Previous studies have individually shown the antidiabetic potential of gamma conglutin (Cγ) and lupanine from lupins. Until now, the influence of combining both compounds and the effective dose of the combination have not been assessed. Moreover, the resulting gene expression profile from this novel combination remains to be explored. Therefore, we aimed to evaluate different dose combinations of Cγ and lupanine by the oral glucose tolerance test (OGTT) to identify the higher antidiabetic effect on a T2D rat model. Later, we administered the selected dose combination during a week. Lastly, we evaluated biochemical parameters and liver gene expression profile using DNA microarrays and bioinformatic analysis. We found that the combination of 28 mg/kg BW Cγ + 20 mg/kg BW lupanine significantly reduced glycemia and lipid levels. Moreover, this treatment positively influenced the expression of Pdk4, G6pc, Foxo1, Foxo3, Ppargc1a, Serpine1, Myc, Slc37a4, Irs2, and Igfbp1 genes. The biological processes associated with these genes are oxidative stress, apoptosis regulation, and glucose and fatty-acid homeostasis. For the first time, we report the beneficial in vivo effect of the combination of two functional lupin compounds. Nevertheless, further studies are needed to investigate the pharmacokinetics and pharmacodynamics of the Cγ + lupanine combined treatment.

2.
Biomolecules ; 11(11)2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34827656

RESUMO

Animal digestive systems host microorganism ecosystems, including integrated bacteria, viruses, fungi, and others, that produce a variety of compounds from different substrates with healthy properties. Among these substrates, α-galacto-oligosaccharides (GOS) are considered prebiotics that promote the grow of gut microbiota with a metabolic output of Short Chain Fatty Acids (SCFAs). In this regard, we evaluated Lupinus albus GOS (LA-GOS) as a natural prebiotic using different animal models. Therefore, the aim of this work was to evaluate the effect of LA-GOS on the gut microbiota, SCFA production, and intestinal health in healthy and induced dysbiosis conditions (an ulcerative colitis (UC) model). Twenty C57BL/6 mice were randomly allocated in four groups (n = 5/group): untreated and treated non-induced animals, and two groups induced with 2% dextran sulfate sodium to UC with and without LA-GOS administration (2.5 g/kg bw). We found that the UC treated group showed a higher goblet cell number, lower disease activity index, and reduced histopathological damage in comparison to the UC untreated group. In addition, the abundance of positive bacteria to butyryl-CoA transferase in gut microbiota was significantly increased by LA-GOS treatment, in healthy conditions. We measured the SCFA production with significant differences in the butyrate concentration between treated and untreated healthy groups. Finally, the pH level in cecum feces was reduced after LA-GOS treatment. Overall, we point out the in vivo health benefits of LA-GOS administration on the preservation of the intestinal ecosystem and the promotion of SCFA production.


Assuntos
Microbioma Gastrointestinal , Animais , Ecossistema , Lupinus , Camundongos
3.
Food Sci Nutr ; 9(5): 2549-2560, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34026071

RESUMO

Although studies on lupin protein isolate (LPI) have indicated the presence of a preventive effect on insulin resistance (IR) and lipid disturbances, their influence on established pathological traits has received little attention. Here, we evaluated the in vivo effects of LPI on IR and steatohepatitis as well as its influence on genes involved in lipid and carbohydrate metabolism. We first induced IR and steatohepatitis in rats by maintaining them on a high-fat diet for 5 weeks. Thereafter, we administered LPI to the rats daily for 3 weeks. LPI improved insulin sensitivity (AUC: 6,777 ± 232 vs. 4,971 ± 379, p < .05, pre- vs. post-treatment values) and reduced glucose and triglyceride levels by one-third. In addition, LPI-treated rats exhibited attenuated steatohepatitis. At the molecular level, LPI treatment reduced liver Fasn gene expression substantially but increased Gys2 and Gsk3b levels. We concluded that the hypolipidemic and hypoglycemic activities of LPI may be caused by reduced liver lipogenesis and modulation of insulin sensitization mechanisms.

4.
Pharm Biol ; 59(1): 374-380, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33784492

RESUMO

CONTEXT: Gamma conglutin (Cγ) from lupine species represents a potential complementary treatment for type 2 diabetes mellitus (T2DM) because of its hypoglycaemic effect. However, its underlying mechanism of action is not fully known. OBJECTIVE: To evaluate whether Cγ from Lupinus rotundiflorus M. E. Jones (Fabaceae) modulates c-Jun N-terminal kinase 1 (JNK1) expression and activation in a T2DM rat model. MATERIALS AND METHODS: Gamma conglutin isolated from L. rotundiflorus seeds was characterized by SDS-PAGE. Fifteen Wistar rats with streptozotocin-induced T2DM (HG) were randomized into three groups (n = 5): vehicle administration (HG-Ctrl), oral treatment with Cγ (120 mg/kg/day) (HG-Lr) for one week, and treatment with metformin (300 mg/kg/day) (HG-Met); a healthy group (Ctrl, n = 5) was included as control. The levels of glucose and biomarkers of renal and hepatic function were measured pre- and post-treatment. Hepatic Jnk1 expression and phosphorylation of JNK1 were evaluated by qRT-PCR and western blot, respectively. RESULTS: Oral treatment with either Cγ or metformin reduced serum glucose level to 86.30 and 74.80 mg/dL, respectively (p ˂ 0.05), from the basal levels. Jnk1 expression was 0.65- and 0.54-fold lower (p ˂ 0.05) in the HG-Lr and HG-Met groups, respectively, than in HG-Ctrl. Treatment with Cγ decreased JNK1 phosphorylation. However, Cγ did not change the levels of kidney and liver biomarkers. DISCUSSION AND CONCLUSIONS: Treatment with Cγ from L. rotundiflorus inhibited Jnk1 expression, in vivo, suggesting JNK1 as a potential therapeutic target in diabetes and revealing one mechanism underlying the hypoglycaemic effect of lupine Cγ. Nevertheless, further studies are required.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Lupinus/química , Proteínas de Plantas/farmacologia , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Masculino , Metformina/farmacologia , Proteína Quinase 8 Ativada por Mitógeno/genética , Proteínas de Plantas/isolamento & purificação , Ratos , Ratos Wistar , Estreptozocina
5.
Biomed Pharmacother ; 133: 110969, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33166762

RESUMO

Constituents of lupin seeds, like γ-conglutin and lupanine, have gained attention as potential complementary treatments for dysglycaemia management. Notwithstanding, the effect of other lupin components on carbohydrate metabolism, including ß-conglutin protein, has received little attention. Here, we investigated the influence of the acute and chronic administration of ß-conglutin on glycaemia modulation in normal and streptozotocin induced-to-diabetes rats. We analysed the liver transcriptome modulation exerted by ß-conglutin in diabetes-induced rats using DNA microarrays to scout for potential molecular targets and pathways involved in this biological response. The acute administration of ß-conglutin reduced the incremental area under the curve of glycaemia in normal and diabetes-induced animals. In a seven-day study with diabetic animals, glycaemia increased significantly in non-treated animals but remained unchanged in animals treated with a daily dose of ß-conglutin. Total cholesterol was significantly lower at the end of the experimental period (-21.8 %, p = 0.039). The microarray and gene ontology analyses revealed several targets and pathways potentially modulated by ß-conglutin treatment, including a possible down-regulation of Jun kinase activity. Moreover, our data indicate that targets related to oxidative stress, inflammation, and estrogenic activity might orchestrate these metabolic effects. In conclusion, our findings show that ß-conglutin may help manage postprandial glycaemia and reduce cholesterol levels under the dysglycaemia stage. We identified and proposed new potential molecular targets for further research related to the mechanism of action of ß-conglutin.


Assuntos
Anticolesterolemiantes/farmacologia , Glicemia/efeitos dos fármacos , Colesterol/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Fígado/efeitos dos fármacos , Lupinus , Extratos Vegetais/farmacologia , Proteínas de Plantas/farmacologia , Proteínas de Armazenamento de Sementes/farmacologia , Transcriptoma/efeitos dos fármacos , Animais , Anticolesterolemiantes/isolamento & purificação , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/genética , Redes Reguladoras de Genes , Hipoglicemiantes/isolamento & purificação , Fígado/metabolismo , Lupinus/química , Masculino , Extratos Vegetais/isolamento & purificação , Proteínas de Plantas/isolamento & purificação , Ratos Wistar , Estreptozocina
6.
Gene ; 761: 145036, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32777525

RESUMO

Lupinus albus γ-conglutin is proposed to positively affect glucose metabolism through inhibition of hepatic glucose production and insulin-mimetic activity; however, the action mechanism is not entirely known. Besides, most studies had focused on its effect on molecular targets directly related to glucose metabolism, and few studies have investigated how γ-conglutin may affect the liver gene expression or if it plays a role in other metabolic processes. Therefore, we investigated the influence of γ-conglutin on the liver transcriptome of streptozotocin-induced diabetic rats using DNA microarrays, ontological analyses, and quantitative PCR. Of the 22,000 genes evaluated, 803 and 173 were downregulated and upregulated, respectively. The ontological analyses of the differentially expressed genes revealed that among others, the mitochondria, microtubules, cytoskeleton, and oxidoreductase activity terms were enriched, implying a possible role of γ-conglutin on autophagy. To corroborate the microarray results, we selected and quantified, by PCR, the expression of two genes associated with autophagy (Atg7 and Snx18) and found their expression augmented two and threefold, respectively; indicating a higher autophagy activity in animals treated with γ-conglutin. Although complementary studies are required, our findings indicate for the first time that the hypoglycaemic effects of γ-conglutin may involve an autophagy induction mechanism, a pivotal process for the preservation of cell physiology and glucose homeostasis.


Assuntos
Colectinas/farmacologia , Lupinus/metabolismo , Soroglobulinas/farmacologia , Transcriptoma/genética , Animais , Glicemia/metabolismo , Colectinas/metabolismo , Colectinas/fisiologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Insulina/metabolismo , Fígado/metabolismo , Fígado/patologia , Lupinus/genética , Masculino , Proteínas de Plantas/genética , Ratos , Ratos Wistar , Sementes/metabolismo , Soroglobulinas/metabolismo , Soroglobulinas/fisiologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-32276385

RESUMO

This study examines the relationship beween employment and psychosocial working conditions and well-being of native and migrant workers in the working population of Spain. Data from the 7th Spanish Survey of Working Conditions was used to conduct a confirmatory factor analysis (n = 8508) to identify the main latent variables that influenced well-being. Using structural equation modeling and multivariate analysis, we found different patterns and perceptions of well-being and working conditions in these two groups. We discuss the reasons for these differences and suggest directions for further research in this area.


Assuntos
Emprego , Migrantes , Adolescente , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espanha , Inquéritos e Questionários , Migrantes/psicologia , Adulto Jovem
8.
Nutrients ; 11(8)2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31382375

RESUMO

As a source of bioactive compounds, species of the genus Lupinus are interesting legumes from a nutritional point of view. Although wild species are abundant and represent a potential source of nutrients and biologically active compounds, most research has focused on domesticated and semi-domesticated species, such as Lupinus angustifolius, Lupinus albus, Lupinus luteus, and Lupinus mutabilis. Therefore, in this review, we focus on recent research conducted on the wild Lupinus species of Mexico. The nutritional content of these species is characterized (similar to those of the domesticated species), including proteins (isolates), lipids, minerals, dietary fiber, and bioactive compounds, such as oligosaccharides, flavonoids, and alkaloids.


Assuntos
Lupinus/química , Valor Nutritivo , Compostos Fitoquímicos/análise , Disponibilidade Biológica , Fibras na Dieta/análise , Humanos , México , Minerais/análise , Proteínas de Vegetais Comestíveis/análise , Prebióticos/análise , Sementes
9.
Rev. bras. farmacogn ; 28(6): 716-723, Nov.-Dec. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-977739

RESUMO

ABSTRACT Recently, lupin seed (Lupinus albus L., Fabaceae) products have emerged as a functional food due to their nutritional and health benefits. Numerous reports have demonstrated the hypoglycemic effects of lupin's gamma conglutin protein; nonetheless, its mechanism of action remains elusive. To understand the role of this protein on glucose metabolism, we evaluated the effect of administering L. albus' gamma conglutin on Slc2a2, Gck, and Pdx-1 gene expression as well as GLUT2 protein tissue levels in streptozotocin-induced diabetic rats. While consuming their regular diet, animals received a daily gamma conglutin dose (120 mg/kg per body weight) for seven consecutive days. Serum glucose levels were measured at the beginning and at the end of the experimental period. At the end of the trial, we quantified gene expression in pancreatic and hepatic tissues as well as GLUT2 immunopositivity in Langerhans islets. Gamma conglutin administration lowered serum glucose concentration by 17.7%, slightly increased Slc2a2 and Pdx-1 mRNA levels in pancreas, up-regulated Slc2a2 expression in the liver, but it had no effect on hepatic Gck expression. After gamma conglutin administration, GLUT2 immunopositivity in Langerhans islets of diabetic animals resembled that of healthy rats. In conclusion, our results indicate that gamma conglutin up-regulates Slc2a2 gene expression in liver and normalizes GLUT2 protein content in pancreas of streptozotocin-induced rats.

10.
Plant Foods Hum Nutr ; 72(2): 134-140, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28101822

RESUMO

Lupinus albus seeds contain conglutin gamma (Cγ) protein, which exerts a hypoglycemic effect and positively modifies proteins involved in glucose homeostasis. Cγ could potentially be used to manage patients with impaired glucose metabolism, but there remains a need to evaluate its effects on hepatic glucose production. The present study aimed to analyze G6pc, Fbp1, and Pck1 gene expressions in two experimental animal models of impaired glucose metabolism. We also evaluated hepatic and renal tissue integrity following Cγ treatment. To generate an insulin resistance model, male Wistar rats were provided 30% sucrose solution ad libitum for 20 weeks. To generate a type 2 diabetes model (STZ), five-day-old rats were intraperitoneally injected with streptozotocin (150 mg/kg). Each animal model was randomized into three subgroups that received the following oral treatments daily for one week: 0.9% w/v NaCl (vehicle; IR-Ctrl and STZ-Ctrl); metformin 300 mg/kg (IR-Met and STZ-Met); and Cγ 150 mg/kg (IR-Cγ and STZ-Cγ). Biochemical parameters were assessed pre- and post-treatment using colorimetric or enzymatic methods. We also performed histological analysis of hepatic and renal tissue. G6pc, Fbp1, and Pck1 gene expressions were quantified using real-time PCR. No histological changes were observed in any group. Post-treatment G6pc gene expression was decreased in the IR-Cγ and STZ-Cγ groups. Post-treatment Fbp1 and Pck1 gene expressions were reduced in the IR-Cγ group but increased in STZ-Cγ animals. Overall, these findings suggest that Cγ is involved in reducing hepatic glucose production, mainly through G6pc inhibition in impaired glucose metabolism disorders.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Lupinus/química , Proteínas de Plantas/administração & dosagem , Animais , Glicemia/efeitos dos fármacos , Proteínas de Ligação a DNA/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Glucose-6-Fosfatase/efeitos dos fármacos , Glucose-6-Fosfatase/metabolismo , Insulina/metabolismo , Resistência à Insulina , Peptídeos e Proteínas de Sinalização Intracelular/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Fosfoenolpiruvato Carboxiquinase (GTP)/efeitos dos fármacos , Fosfoenolpiruvato Carboxiquinase (GTP)/metabolismo , Ratos , Ratos Wistar , Sementes/química , Estreptozocina/efeitos adversos
11.
Exp Toxicol Pathol ; 69(1): 27-31, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27825754

RESUMO

Sparteine is one of the most toxic quinolizidine alkaloids found in leguminous plants. Several studies have demonstrated that sparteine affects the nervous system, blocking the nervous ganglion, producing antimuscarinic effects, depressing the central nervous system and causing neuronal necrosis. However, there are no reports identifying the areas of the brain that are sensitive to the toxic effects of this alkaloid. 32 adult Wistar rats were on study, sixteen were implanted with an intracerebral stainless steel cannula and randomly assigned to a control or experimental group (n=8). Animals, control and experimental, received daily intraventricular (ICV) injections of a sparteine or a sterile water solution for five consecutive days. Additionally, two groups of animals (8 rats each) received daily intraperotineal injections (IP) of a sparteine or sterile water solution for five consecutive days. 72h after the last dose, the animals were sacrificed, their brains removed, fixed and embedded in paraffin to obtain 10µm tissue slices. Brain slices were stained with H&E and evaluated under a light microscope. The main brain structures sensitive to sparteine were the cerebral cortex (frontal, fronto-parietal and striate) olfactory and amygdaloid areas, the ventromedial hypothalamic nucleus, the Purkinje cells in the cerebellum, and the CA1, CA3 and dentate gyrus regions of the hippocampus. Administration of sparteine, via ICV or IP, caused neuronal necrosis in brain structures, mainly related with cholinergic pathways.


Assuntos
Antiarrítmicos/toxicidade , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Esparteína/toxicidade , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar
12.
Rev Esp Enferm Dig ; 107(12): 732-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26671585

RESUMO

OBJECTIVE: The purpose of this study was to assess the resectability and effectiveness of repeat hepatectomy for relapsing liver metastases of colorectal origin in terms of morbidity, mortality, overall survival, and disease-free survival. METHODS: A retrospective study was performed on a prospective cohort of patients with colorectal liver metastases who underwent repeat surgery at Hospital Universitario San Cecilio, Granada (Spain), from March 2003 to June 2013. Primary outcome variables included survival and morbidity within 30 days post-surgery. RESULTS: A total of 147 patients with colorectal liver metastases underwent surgical excision during the study period; 61 patients had liver recurrence, and 34 of these received repeat surgery. The overall survival rate at 5 and 10 years for resected patients (n=27/34) was 48% and 48%. Mean hospital stay was 8.9 ± 3.5 days, morbidity was 9%, and mortality was 0%. CONCLUSION: Repeat liver resection for colorectal liver metastases is a safe, effective surgical procedure whose results are similar to those obtained after initial liver resection.


Assuntos
Neoplasias Colorretais/patologia , Hepatectomia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/secundário , Recidiva Local de Neoplasia/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Reoperação , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
13.
Rev. esp. enferm. dig ; 107(12): 732-739, dic. 2015. tab, ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-146740

RESUMO

OBJETIVO: el objetivo de este estudio es evaluar la resecabilidad efectividad de las rehepatectomías en metástasis hepáticas de origen colorrectal recidivadas en términos de morbimortalidad, supervivencia global y libre de enfermedad. MÉTODOS: se realizó un estudio retrospectivo de una cohorte prospectiva de pacientes con metástasis hepáticas de origen colorrectal con cirugía de repetición en el Hospital Universitario San Cecilio de Granada de marzo de 2003 hasta junio de 2013. Las variables principales de resultado fueron la supervivencia y la morbilidad antes de los 30 días del postoperatorio. RESULTADOS: un total de 147 pacientes con metástasis hepáticas de origen colorrectal se sometieron a la extirpación quirúrgica durante el periodo de estudio; 61 pacientes presentaron una recidiva hepática de los cuales 34 se sometieron a una cirugía de repetición. La tasa global de supervivencia a 5 y 10 años para los pacientes resecados fue del 48 y el 48%. La estancia media hospitalaria fue de 8,9 ± 3,5 días, la morbilidad del 9% y la mortalidad del 0%. CONCLUSIÓN: las resecciones hepáticas repetidas para las metástasis hepáticas de origen colorrectal constituyen una operación segura y eficaz, con resultados similares a los obtenidos tras una primera resección hepática


OBJECTIVE: The purpose of this study was to assess the resectability and effectiveness of repeat hepatectomy for relapsing liver metastases of colorectal origin in terms of morbidity, mortality, overall survival, and disease-free survival. METHODS: A retrospective study was performed on a prospective cohort of patients with colorectal liver metastases who underwent repeat surgery at Hospital Universitario San Cecilio, Granada (Spain), from March 2003 to June 2013. Primary outcome variables included survival and morbidity within 30 days post-surgery. RESULTS: A total of 147 patients with colorectal liver metastases underwent surgical excision during the study period; 61 patients had liver recurrence, and 34 of these received repeat surgery. The overall survival rate at 5 and 10 years for resected patients (n=27/34) was 48% and 48%. Mean hospital stay was 8.9 ± 3.5 days, morbidity was 9%, and mortality was 0%. CONCLUSION: Repeat liver resection for colorectal liver metastases is a safe, effective surgical procedure whose results are similar to those obtained after initial liver resection


Assuntos
Humanos , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/cirurgia , Hepatectomia/estatística & dados numéricos , Metástase Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Hepáticas/secundário , Reoperação/estatística & dados numéricos , Taxa de Sobrevida , Resultado do Tratamento
14.
Molecules ; 20(10): 19085-100, 2015 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-26492234

RESUMO

The glucose-lowering effects of lupin seeds involve the combined action of several components. The present study investigates the influence of one of the main quinolizidine alkaloids, lupanine, on pancreatic beta cells and in an animal model of type-2 diabetes mellitus. In vitro studies were performed with insulin-secreting INS-1E cells or islets of C57BL/6 mice. In the in vivo experiments, hyperglycemia was induced in rats by injecting streptozotocin (65 mg/kg body weight). In the presence of 15 mmol/L glucose, insulin secretion was significantly elevated by 0.5 mmol/L lupanine, whereas the alkaloid did not stimulate insulin release with lower glucose concentrations. In islets treated with l-arginine, the potentiating effect of lupanine already occurred at 8 mmol/L glucose. Lupanine increased the expression of the Ins-1 gene. The potentiating effect on secretion was correlated to membrane depolarization and an increase in the frequency of Ca(2+) action potentials. Determination of the current through ATP-dependent K⁺ channels (KATP channels) revealed that lupanine directly inhibited the channel. The effect was dose-dependent but, even with a high lupanine concentration of 1 mmol/L or after a prolonged exposure time (12 h), the KATP channel block was incomplete. Oral administration of lupanine did not induce hypoglycemia. By contrast, lupanine improved glycemic control in response to an oral glucose tolerance test in streptozotocin-diabetic rats. In summary, lupanine acts as a positive modulator of insulin release obviously without a risk for hypoglycemic episodes.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Insulina/genética , Canais KATP/efeitos dos fármacos , Esparteína/análogos & derivados , Animais , Arginina/administração & dosagem , Arginina/farmacologia , Glicemia/metabolismo , Diabetes Mellitus Experimental/genética , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Esparteína/administração & dosagem , Esparteína/farmacologia , Estreptozocina
15.
Plant Foods Hum Nutr ; 69(3): 241-7, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24894193

RESUMO

Several studies support the health-promoting benefits of lupins, particularly lupin proteins. It has been demonstrated that Lupinus albus gamma conglutin (Cγ) protein lowered blood glucose levels; thus, Cγ showed promise as a new anti-diabetic compound for type 2 diabetes (T2D) treatment. The aim of this study was to evaluate the effect of Cγ on Ins-1 gene expression and on pancreatic insulin content in streptozotocin-mediated diabetic rats. Cγ was isolated from Lupinus albus seeds. Its identification was confirmed with polyacrylamide gel electrophoresis under native and denaturing conditions. We used streptozotocin (STZ) to induce T2D on the 5th day of life of newborn male Wistar rats (n5-STZ). After 20 weeks post-induction, these animals (glycemia > 200 mg/dL) were randomly assigned to three groups that received the following one-week treatments: vehicle, 0.90% w/v NaCl (n5 STZ-Ctrl); glibenclamide, 10 mg/kg (n5 STZ-Glib); or Cγ, 120 mg/kg (n5 STZ-Cγ). Glucose and insulin levels were measured before and after treatment. Ins-1 gene expression was quantified using real time polymerase chain reaction and the pancreatic insulin content was evaluated with immunohistochemistry. Post-treatment, the n5 STZ-Cγ and n5 STZ-Glib groups showed reductions in glucose, increments in serum insulin, and increases in Ins-1 gene expression and beta cell insulin content compared to the n5 STZ-Ctrl group. The results showed that Cγ had beneficial effects on Ins-1 gene expression and pancreatic insulin content. These biological effects of Cγ strengthen its promising potential as a nutraceutical and/or new agent for controlling hyperglycemia.


Assuntos
Expressão Gênica , Hipoglicemiantes/administração & dosagem , Insulina/genética , Lupinus/química , Pâncreas/metabolismo , Proteínas de Plantas/administração & dosagem , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glibureto/administração & dosagem , Insulina/metabolismo , Células Secretoras de Insulina , Masculino , Extratos Vegetais/administração & dosagem , Ratos , Ratos Wistar , Estreptozocina
16.
Histol Histopathol ; 29(11): 1415-21, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24723146

RESUMO

The aim of this study was to determine the flavonoid profile of Lupinus mexicanus germinated seed extract (PE) and to evaluate its effect as a phytoestrogen on the morphometric parameters of CA3 hippocampal neurons of ovariectomized rats (OVX). L. mexicanus seeds, germinated for 48 h, were homogenized and macerated using an 80% ethanol solution. The extract was analyzed by HPLC/MS-MS. Thirty young Wistar strain female rats (200±10 g) were randomly distributed into four groups: sham operated (S) treated with dimethyl sulfoxide (vehicle); ovariectomized and treated with 1250 µg of PE extract (OVX-PE); ovariectomized and treated with 5 µg estradiol benzoate (OVX-EB); and ovariectomized and vehicle treated (OVX). All substances were injected subcutaneously daily for 28 days. On day 29, the animals were sacrificed, perfused, and fixed to obtain the brains for histological processing. Each brain was cut and stained with hematoxylin and eosin. The thickness of the stratum oriens (SO), the nuclear diameter, and the neuronal density were measured in the hippocampus CA3 area. Nine different flavonoids and one non-identified compound were detected. The histological analysis demonstrated that the thickness of the SO was higher in the OVX-EB and S groups than in the OVX-PE and OVX groups (p⟨0.05); in addition, the nuclear diameters of the neurons in the OVX-EB and S groups were higher compared with the other groups (p⟨0.05). The OVX group had the highest cellular density among groups (p⟨0.05). Based on our results, the PE obtained did not have beneficial effects on CA3 hippocampal neurons.


Assuntos
Flavonoides/química , Lupinus/química , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/química , Extratos Vegetais/química , Sementes/química , Animais , Região CA3 Hipocampal/citologia , Cromatografia Líquida , Estrogênios/química , Feminino , Germinação , Glicoconjugados/química , Espectrometria de Massas , Neurônios/citologia , Fenol/química , Fitoestrógenos/química , Ratos , Ratos Wistar , Extração em Fase Sólida , Espectrofotometria Ultravioleta
17.
Biol Res ; 46(3): 281-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24346076

RESUMO

OBJECTIVE: The high global incidence of type 2 diabetes has challenged researchers to establish animal models that resemble the chronic stage observed in type 2 diabetes patients. One such model is induced by neonatal streptozotocin (n-STZ) administration to rat pups at 0, 2, or 5 days after birth. In this study, we assessed lns-1 gene expression and tissue insulin levels as well as serum concentration of glucose and insulin, insulin resistance, and histological changes of the islets of Langerhans in n5-STZ rats after 20-weeks post-induction. METHODS: Wistar rat pups were randomly distributed into a control group and a streptozotocin-induced group. Experimental induction involved a single intraperitoneal injection of streptozotocin (150 mg/kg) into neonates at five days after birth. RESULTS: At 20 weeks post-induction, streptozotocin-induced rats exhibited increased serum glucose levels, reduced serum insulin levels, impaired glucose metabolism and insulin resistance compared to control rats. Histologically, streptozotocin-induced rats exhibited atrophic islets, vacuolization, and significantly fewer insulin-positive cells. lns-1 gene expression was significantly decreased in n5-STZ rats in comparison to the control group. CONCLUSION: Our findings support that the n5-STZ model 20 weeks post-induction represents an appropriate experimental tool to study T2D and to evaluate novel therapeutic agents and targets that involve insulin gene expression and secretion, as well as complications caused by chronic diabetes.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Regulação da Expressão Gênica , Insulina/genética , Ilhotas Pancreáticas/metabolismo , Animais , Animais Recém-Nascidos , Diabetes Mellitus Experimental/induzido quimicamente , Modelos Animais de Doenças , Feminino , Imuno-Histoquímica , Insulina/metabolismo , Resistência à Insulina , Distribuição Aleatória , Ratos , Ratos Wistar , Estreptozocina , Fatores de Tempo
18.
Nutr Hosp ; 28(3): 779-86, 2013.
Artigo em Espanhol | MEDLINE | ID: mdl-23848103

RESUMO

OBJECTIVES: The main research objective was to analyze the intake of macronutrients and micronutrients in a population of adolescents. The purpose of the study was to verify a significant correlation between the habit of breafasting at home each morning and the nutritional status of the sample population. SAMPLE AND METHODOLOGY: The sample population was composed of 100 adolescents, 12-15 years of age, who attended two public secondary schools in the city of Granada. The study conducted was descriptive, cross-sectional, and multi-centered, and involved a comprehensive evaluation of the nutritional status of the subjects by using anthropometry. The analysis of food intake and dietary habits was based on a 72-hour record of the subjects' food intake. The protocol used had previously been elaborated and validated by the research team. RESULTS: For all subjects, the energy intake was found to be higher than the recommended dietary allowance (RDA). The female subjects had a mean protein intake of 16% in regards to total calorific value (TCV). In the case of the male subjects, the mean protein intake was 15%. The mean consumption of fats was 106.1 for the male subjects, whereas for the females, it was 110.4 grams. The females were found to ingest more carbohydrates at a rate of 297.4 grams per day in comparison to the male subjects, whose rate of carbohydrate ingestion was 251 grams per day. The ingestion of minerals varied in both sexes though in all cases it was lower than the RDA. However, the male subjects had a calcium and zinc intake higher than the RDA for these minerals. The vitamin intake was varied and balanced in both male and female subjects, and covered the requirements for both age and sex. Regarding the variable, breakfast, a significant relation was found (p < 0.0001) between the dietary habit of breakfasting at home before going to school and the nutritional status of the students. CONCLUSIONS: The results of this study showed that an optimal nutritional and health status requires a balanced food intake and healthy dietary habits.


Objetivos: Los objetivos de este estudio fueron realizar un análisis de la ingesta de macronutrientes y micronutrientes en una población de adolescentes. En segundo lugar, verificar una correlación significativa entre el hábito de desayunar a diario en casa y el estado nutricional de dicha población. Muestra y metodología: La población de estudio estaba compuesta por 100 adolescentes de entre 12 y 15 años de edad, pertenecientes a 2 centros educativos públicos de la ciudad de Granada. Estudio descriptivo, transversal y multicéntrico en el que se llevó a cabo una valoración completa del estado nutricional de los alumnos mediante antropometría. Para el análisis de la ingesta alimentaria y hábitos nutricionales se utilizó un registro alimentario de 72 horas, específicamente elaborado y validado por el equipo investigador. Resultados: La ingesta energética fue superior en ambos sexos a la recomendada por la RDA. Se encontró una ingesta proteica media en chicas del 16% respecto del valor calórico total (VCT) y de un 15% del VCT en varones. Se evidenció un consumo medio de grasas de (106,1 gramos) en chicos, frente a los 100,4 gramos en chicas. Éstas ingerían más carbohidratos, destacando una ingesta media de 279,4 gramos/día frente a los 251 gramos/día ingeridos en varones. La ingesta de minerales fue variable en ambos sexos, siendo inferior a las recomendaciones de la RDA en chicas. En los varones resaltó una ingesta de calcio y zinc por encima de dichas recomendaciones. El aporte vitamínico fue variado y equilibrado en ambos sexos, cubriendo los requerimientos para edad y sexo. Respecto de la variable desayuno, se encontró una relación significativa (p < 0,0001) entre el hábito de desayunar en casa, antes de ir al instituto y el estado nutricional de los alumnos. Conclusiones: Un óptimo estado nutricional y de salud implica necesariamente mantener una alimentación equilibrada en sus nutrientes y unos hábitos nutricionales saludables.


Assuntos
Ingestão de Alimentos , Comportamento Alimentar , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Estado Nutricional , Espanha , Saúde da População Urbana
19.
Nutr. hosp ; 28(3): 779-786, mayo-jun. 2013. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-120053

RESUMO

Objetivos: Los objetivos de este estudio fueron realizar un análisis de la ingesta de macronutrientes y micronutrientes en una población de adolescentes. En segundo lugar, verificar una correlación significativa entre el hábito de desayunar a diario en casa y el estado nutricional de dicha población. Muestra y metodología: La población de estudio estaba compuesta por 100 adolescentes de entre 12 y 15 años de edad, pertenecientes a 2 centros educativos públicos de la ciudad de Granada. Estudio descriptivo, transversal y multicéntrico en el que se llevó a cabo una valoración completa del estado nutricional de los alumnos mediante antropometría. Para el análisis de la ingesta alimentaria y hábitos nutricionales se utilizó un registro alimentario de 72 horas, específicamente elaborado y validado por el equipo investigador. Resultados: La ingesta energética fue superior en ambos sexos a la recomendada por la RDA. Se encontró una ingesta proteica media en chicas del 16% respecto del valor calórico total (VCT) y de un 15% del VCT en varones. Se evidenció un consumo medio de grasas de (106,1 gramos) en chicos, frente a los 100,4 gramos en chicas. Éstas ingerían más carbohidratos, destacando una ingesta media de 279,4 gramos/día frente a los 251 gramos/día ingeridos en varones. La ingesta de minerales fue variable en ambos sexos, siendo inferior a las recomendaciones de la RDA en chicas. En los varones resaltó una ingesta de calcio y zinc por encima de dichas recomendaciones. El aporte vitamínico fue variado y equilibrado en ambos sexos, cubriendo los requerimientos para edad y sexo. Respecto de la variable desayuno, se encontró una relación significativa (p < 0,0001) entre el hábito de desayunar en casa, antes de ir al instituto y el estado nutricional de los alumnos. Conclusiones: Un óptimo estado nutricional y de salud implica necesariamente mantener una alimentación equilibrada en sus nutrientes y unos hábitos nutricionales saludables. (AU)


Objectives: The main research objective was to analyze the intake of macronutrients and micronutrients in a population of adolescents. The purpose of the study was to verify a significant correlation between the habit of breafasting at home each morning and the nutritional status of the sample population. Sample and methodology: The sample population was composed of 100 adolescents, 12-15 years of age, who attended two public secondary schools in the city of Granada. The study conducted was descriptive, cross-sectional, and multi-centered, and involved a comprehensive evaluation of the nutritional status of the subjects by using anthropometry. The analysis of food intake and dietary habits was based on a 72-hour record of the subjects' food intake. The protocol used had previously been elaborated and validated by the research team. Results: For all subjects, the energy intake was found to be higher than the recommended dietary allowance (RDA). The female subjects had a mean protein intake of 16% in regards to total calorific value (TCV). In the case of the male subjects, the mean protein intake was 15%. The mean consumption of fats was 106.1 for the male subjects, whereas for the females, it was 110.4 grams. The females were found to ingest more carbohydrates at a rate of 297.4 grams per day in comparison to the male subjects, whose rate of carbohydrate ingestion was 251 grams per day. The ingestion of minerals varied in both sexes though in all cases it was lower than the RDA. However, the male subjects had a calcium and zinc intake higher than the RDA for these minerals. The vitamin intake was varied and balanced in both male and female subjects, and covered the requirements for both age and sex. Regarding the variable, breakfast, a significant relation was found (p < 0.0001) between the dietary habit of breakfasting at home before going to school and the nutritional status of the students. Conclusions: The results of this study showed that an optimal nutritional and health status requires a balanced food intake and healthy dietary habits (AU)


Assuntos
Humanos , Masculino , Feminino , Adolescente , Comportamento Alimentar , Ingestão de Alimentos , 24457 , Transtornos da Nutrição Infantil/prevenção & controle , Alimentos Integrais , Estado Nutricional
20.
Phytochemistry ; 92: 71-86, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23642387

RESUMO

Flavonoid glycoconjugates from roots and leaves of eight North America lupine species (Lupinus elegans, Lupinus exaltatus, Lupinus hintonii, Lupinus mexicanus, Lupinus montanus, Lupinus rotundiflorus, Lupinus stipulatus, Lupinus sp.), three Mediterranean species (Lupinus albus, Lupinus angustifolius, Lupinus luteus) and one species from South America domesticated in Europe (Lupinus mutabilis) were analyzed using two LC/MS systems: low-resolution ion trap instrument and high-resolution quadrupole-time-of-flight spectrometer. As a result of the LC/MS profiling using the CID/MS(n) experiments structures of 175 flavonoid glycoconjugates found in 12 lupine species were identified at three confidence levels according to the Metabolomic Standard Initiative, mainly at level 2 and 3, some of them were classified to the level 1. Among the flavonoid derivatives recognized in the plant extracts were isomeric or isobaric compounds, differing in the degree of hydroxylation of the aglycones and the presence of glycosidic, acyl or alkyl groups in the molecules. The elemental composition of the glycoconjugate molecules was established from the exact m/z values of the protonated/deprotonated molecules ([M+H](+)/[M-H](-)) measured with the accuracy better than 5 ppm. Information concerning structures of the aglycones, the type of sugar moieties (hexose, deoxyhexose or pentose) and, in some cases, their placement on the aglycones as well as the acyl substituents of the flavonoid glycoconjugates was achieved in experiments, in which collision-induced dissociation was applied. Flavonoid aglycones present in the studied O-glycoconjugates were unambiguously identified after the comparison of the pseudo-MS(3) spectra with the spectra registered for the standards. Isomers of flavonoid glycoconjugates, in which one or two sugar moieties were attached to 4'- or 7-hydroxyl groups or directly to the C-6 or C-8 of the aglycones, could be distinguished on the basis of the MS(2) spectra. However, the collision energy applied in the CID experiments had to be optimized for each group of the compounds and there were no universal settings that allowed the acquisition of structural information for all the compounds present in the sample. Information obtained from the flavonoid conjugate profiling was used for the chemotaxonomic comparison of the studied lupine species. A clear-cut discrimination of the Mediterranean and North American lupines was obtained as a result of this analysis.


Assuntos
Lupinus/química , Fenóis/análise , Fenóis/metabolismo , Cromatografia Líquida , Espectrometria de Massas , México , Estrutura Molecular , Especificidade da Espécie
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