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Basic research on types 1 and 2 diabetes mellitus require early stage studies using beta cells or cell lines, ideally of human origin and with preserved insulin secretion in response to glucose. The 1.1E7 cells are a hybrid cell line resulting from the electrofusion of dispersed human islets and PANC-1 cells, capable of secreting insulin in response to glucose, but their survival and function under toxic conditions remains untested. This characterization is the purpose of the present study. We treated these cells with a cytokine mix, high glucose, palmitate, and the latter two combined. Under these conditions, we measured cell viability and apoptosis (MTT, Caspase Glo and TUNEL assays, as well as caspase-8 and -9 levels by Western blotting), endoplasmic reticulum stress markers (EIF2AK3, HSPA4, EIF2a, and HSPA5) by real-time PCR, and insulin secretion with a glucose challenge. All of these stimuli (i) induce apoptosis and ER stress markers expression, (ii) reduce mRNA amounts of 2–5 components of genes involved in the insulin secretory pathway, and (iii) abrogate the insulin release capability of 1.1E7 cells in response to glucose. The most pronounced effects were observed with cytokines and with palmitate and high glucose combined. This characterization may well serve as the starting point for those choosing this cell line for future basic research on certain aspects of diabetes.
Antonia Diaz-Ganete; Aranzazu Quiroga-De-Castro; Rosa Mateos; Francisco Medina; Carmen Segundo; Alfonso Lechuga-Sancho. Toxicity Induced by Cytokines, Glucose, and Lipids Increase Apoptosis and Hamper Insulin Secretion in the 1.1E7 Beta Cell-Line. International Journal of Molecular Sciences 2021, 22, 2559 .
AMA StyleAntonia Diaz-Ganete, Aranzazu Quiroga-De-Castro, Rosa Mateos, Francisco Medina, Carmen Segundo, Alfonso Lechuga-Sancho. Toxicity Induced by Cytokines, Glucose, and Lipids Increase Apoptosis and Hamper Insulin Secretion in the 1.1E7 Beta Cell-Line. International Journal of Molecular Sciences. 2021; 22 (5):2559.
Chicago/Turabian StyleAntonia Diaz-Ganete; Aranzazu Quiroga-De-Castro; Rosa Mateos; Francisco Medina; Carmen Segundo; Alfonso Lechuga-Sancho. 2021. "Toxicity Induced by Cytokines, Glucose, and Lipids Increase Apoptosis and Hamper Insulin Secretion in the 1.1E7 Beta Cell-Line." International Journal of Molecular Sciences 22, no. 5: 2559.
This paper describes the protocol for a study designed to address the high prevalence (40%) of childhood overweight and obesity in the province of Cádiz, Spain, as a reflection of what is happening worldwide. It is widely known that children who suffer from childhood obesity have a higher risk of developing chronic diseases in adulthood. This causes a decrease in the quality of life and an increase in health spending. In this context, it is necessary to intervene promoting healthy lifestyle habits from an early stage. The objective of this project will be to evaluate the effectiveness of a multimodal intervention (individual, school and family) called “PREVIENE-CÁDIZ” [CADIZ-PREVENT]. The intervention will be focused mainly on diet, physical activity, sedentary lifestyle and sleep, to prevent overweight and obesity in schoolchildren from 8 to 9 years old in the province of Cádiz. It will consist of a 10-session education program carried out in the classroom by the teachers. In addition, children will be assigned two workbooks, one to work on in class and the other at home with parents. A workshop aimed at parents will be included to help teach them how to obtain healthier lifestyle habits. The proposed study will involve a quasi-experimental design with a control group.
Rubén Aragón-Martín; María Del Mar Gómez-Sánchez; David Jiménez-Pavón; José Manuel Martínez-Nieto; Mónica Schwarz-Rodríguez; Carmen Segundo-Iglesias; José Pedro Novalbos-Ruiz; María José Santi-Cano; José Castro-Piñero; Carmen Lineros-González; Mariano Hernán-García; Amelia Rodríguez-Martín. A Multimodal Intervention for Prevention of Overweight and Obesity in Schoolchildren. A Protocol Study “PREVIENE-CÁDIZ”. International Journal of Environmental Research and Public Health 2021, 18, 1622 .
AMA StyleRubén Aragón-Martín, María Del Mar Gómez-Sánchez, David Jiménez-Pavón, José Manuel Martínez-Nieto, Mónica Schwarz-Rodríguez, Carmen Segundo-Iglesias, José Pedro Novalbos-Ruiz, María José Santi-Cano, José Castro-Piñero, Carmen Lineros-González, Mariano Hernán-García, Amelia Rodríguez-Martín. A Multimodal Intervention for Prevention of Overweight and Obesity in Schoolchildren. A Protocol Study “PREVIENE-CÁDIZ”. International Journal of Environmental Research and Public Health. 2021; 18 (4):1622.
Chicago/Turabian StyleRubén Aragón-Martín; María Del Mar Gómez-Sánchez; David Jiménez-Pavón; José Manuel Martínez-Nieto; Mónica Schwarz-Rodríguez; Carmen Segundo-Iglesias; José Pedro Novalbos-Ruiz; María José Santi-Cano; José Castro-Piñero; Carmen Lineros-González; Mariano Hernán-García; Amelia Rodríguez-Martín. 2021. "A Multimodal Intervention for Prevention of Overweight and Obesity in Schoolchildren. A Protocol Study “PREVIENE-CÁDIZ”." International Journal of Environmental Research and Public Health 18, no. 4: 1622.
The analytical bias introduced by most of the commonly used techniques in metabolomics considerably hinders the simultaneous detection of all metabolites present in complex biological samples. In order to solve this limitation, the combination of complementary approaches is emerging in recent years as the most suitable strategy in order to maximize metabolite coverage. This review article presents a general overview of the most important analytical techniques usually employed in metabolomics: nuclear magnetic resonance, mass spectrometry and hybrid approaches. Furthermore, we emphasize the potential of integrating various tools in the form of metabolomic multi-platforms in order to get a deeper metabolome characterization, for which a revision of the existing literature in this field is provided. This review is not intended to be exhaustive but, rather, to give a practical and concise guide to readers not familiar with analytical chemistry on the considerations to account for the proper selection of the technique to be used in a metabolomic experiment in biomedical research.
Alvaro Gonzalez-Dominguez; Enrique Duran-Guerrero; Angeles Fernandez-Recamales; Alfonso Maria Lechuga-Sancho; Ana Sayago; Monica Schwarz; Carmen Segundo; Raul Gonzalez-Dominguez; Enrique Duran-Guerrero Alvaro Gonzalez-Dominguez. An Overview on the Importance of Combining Complementary Analytical Platforms in Metabolomic Research. Current Topics in Medicinal Chemistry 2018, 17, 3289 -3295.
AMA StyleAlvaro Gonzalez-Dominguez, Enrique Duran-Guerrero, Angeles Fernandez-Recamales, Alfonso Maria Lechuga-Sancho, Ana Sayago, Monica Schwarz, Carmen Segundo, Raul Gonzalez-Dominguez, Enrique Duran-Guerrero Alvaro Gonzalez-Dominguez. An Overview on the Importance of Combining Complementary Analytical Platforms in Metabolomic Research. Current Topics in Medicinal Chemistry. 2018; 17 (30):3289-3295.
Chicago/Turabian StyleAlvaro Gonzalez-Dominguez; Enrique Duran-Guerrero; Angeles Fernandez-Recamales; Alfonso Maria Lechuga-Sancho; Ana Sayago; Monica Schwarz; Carmen Segundo; Raul Gonzalez-Dominguez; Enrique Duran-Guerrero Alvaro Gonzalez-Dominguez. 2018. "An Overview on the Importance of Combining Complementary Analytical Platforms in Metabolomic Research." Current Topics in Medicinal Chemistry 17, no. 30: 3289-3295.
Oxidative stress and inflammation have been postulated as underlying mechanisms for the development of obesity-related insulin resistance. This association however, remains elusive especially in childhood. We sought to investigate this relation by measuring oxidative stress and antioxidant response biomarkers, before and during an oral glucose tolerance test (OGTT), in different biological samples from obese children. 24 children were recruited for the study, (18 obese and 6 controls). After OGTT, the obese group was subdivided in two, according to whether or not carbohydrate metabolic impairment (Ob.IR+, Ob.IR-; respectively) was found. Different biomarkers were analyzed after fasting (T = 0) and during an OGTT (T = 60 and 120 min). Lipoperoxides were measured in plasma, erythrocytes, and urine; while advanced glycation end products were determined in plasma, and redox status (GSH/GSSG ratio) in erythrocytes. We found marked differences in the characterization of the oxidative status in urine and erythrocytes, and in the dynamics of the antioxidant response during OGTT. Specifically, Ob.IR+ children show increased oxidative stress, deficient antioxidant response and a significant imbalance in redox status, in comparison to controls and Ob.IR- children. Obese children with insulin resistance show increased levels of oxidative stress biomarkers, and a stunted antioxidant response to an OGTT leading to increased oxidative stress after a single glucose load, as detected in erythrocytes, but not in plasma. We propose erythrocytes as sensors of early and acute changes in oxidative stress associated with insulin resistance in childhood obesity. This is a pilot study, performed with a limited sample size, so data should be interpreted with caution until reproduced.
Alfonso Lechuga-Sancho; David Gallego-Andujar; Pablo Ruiz-Ocaña; Francisco M. Visiedo; Ana Saez-Benito; Mónica Schwarz; Carmen Segundo; Rosa M. Mateos. Obesity induced alterations in redox homeostasis and oxidative stress are present from an early age. PLOS ONE 2018, 13, e0191547 .
AMA StyleAlfonso Lechuga-Sancho, David Gallego-Andujar, Pablo Ruiz-Ocaña, Francisco M. Visiedo, Ana Saez-Benito, Mónica Schwarz, Carmen Segundo, Rosa M. Mateos. Obesity induced alterations in redox homeostasis and oxidative stress are present from an early age. PLOS ONE. 2018; 13 (1):e0191547.
Chicago/Turabian StyleAlfonso Lechuga-Sancho; David Gallego-Andujar; Pablo Ruiz-Ocaña; Francisco M. Visiedo; Ana Saez-Benito; Mónica Schwarz; Carmen Segundo; Rosa M. Mateos. 2018. "Obesity induced alterations in redox homeostasis and oxidative stress are present from an early age." PLOS ONE 13, no. 1: e0191547.
This work showed an increase in β-cell mass after the resection of an important portion of small bowel. The Roux-Y Gastric Bypass produced a non-significant increase in β-cell mass. We considered that these implications of surgery over the endocrine pancreas must be one of the mechanisms related to the improvement of type 2 Diabetes mellitus following bariatric surgery.
Alonso Camacho-Ramírez; Manuel Blandino-Rosano; M Carmen Segundo-Iglesias; Alfonso M Lechuga-Sancho; Manuel Aguilar-Diosdado; Gonzalo M Pérez-Arana; J Arturo Prada-Oliveira. Bariatric surgery influences β-Cell turnover in non obese rats. Histol. Histopathol. 2017, 32, 1341 -1350.
AMA StyleAlonso Camacho-Ramírez, Manuel Blandino-Rosano, M Carmen Segundo-Iglesias, Alfonso M Lechuga-Sancho, Manuel Aguilar-Diosdado, Gonzalo M Pérez-Arana, J Arturo Prada-Oliveira. Bariatric surgery influences β-Cell turnover in non obese rats. Histol. Histopathol.. 2017; 32 (32):1341-1350.
Chicago/Turabian StyleAlonso Camacho-Ramírez; Manuel Blandino-Rosano; M Carmen Segundo-Iglesias; Alfonso M Lechuga-Sancho; Manuel Aguilar-Diosdado; Gonzalo M Pérez-Arana; J Arturo Prada-Oliveira. 2017. "Bariatric surgery influences β-Cell turnover in non obese rats." Histol. Histopathol. 32, no. 32: 1341-1350.
High sugar consumption elicits numerous deleterious effects on health by inducing insulin resistance, which is closely associated with the development of metabolic disorders such as obesity or type‐2 diabetes. Furthermore, there is also growing evidence that caffeine may play an important role in the regulation of insulin release and the appearance of related metabolic impairments. Thus, the aim of this work was to investigate the impact of acute sugar and caffeine intake on the metabolic health status by using a metabolomic multi‐platform based on the combination of flow injection mass spectrometry and ultra‐high performance liquid chromatography mass spectrometry. To this end, we performed a randomized, crossover and double‐blind intervention study with different soft drinks from the same brand. Numerous metabolomic changes were detected in serum samples over time after the intake of sugar‐sweetened beverages, including energy‐related metabolites, amino acids and lipids, thus demonstrating the intense effects provoked by acute sugar consumption on the organism during 3 h of follow‐up. However, the most significant findings were observed after the co‐ingestion of caffeine, which could be indicative of a synergic effect of this psychostimulant on insulin‐mediated perturbations.
Raúl González‐Domínguez; Rosa María Mateos; Alfonso María Lechuga‐Sancho; Jose Joaquin Gonzalez Cortes; Manuel Corrales-Cuevas; Juan Alberto Rojas-Cots; Carmen Segundo; Mónica Schwarz. Synergic effects of sugar and caffeine on insulin-mediated metabolomic alterations after an acute consumption of soft drinks. ELECTROPHORESIS 2017, 38, 2313 -2322.
AMA StyleRaúl González‐Domínguez, Rosa María Mateos, Alfonso María Lechuga‐Sancho, Jose Joaquin Gonzalez Cortes, Manuel Corrales-Cuevas, Juan Alberto Rojas-Cots, Carmen Segundo, Mónica Schwarz. Synergic effects of sugar and caffeine on insulin-mediated metabolomic alterations after an acute consumption of soft drinks. ELECTROPHORESIS. 2017; 38 (18):2313-2322.
Chicago/Turabian StyleRaúl González‐Domínguez; Rosa María Mateos; Alfonso María Lechuga‐Sancho; Jose Joaquin Gonzalez Cortes; Manuel Corrales-Cuevas; Juan Alberto Rojas-Cots; Carmen Segundo; Mónica Schwarz. 2017. "Synergic effects of sugar and caffeine on insulin-mediated metabolomic alterations after an acute consumption of soft drinks." ELECTROPHORESIS 38, no. 18: 2313-2322.
Dysregulation of NO production is implicated in pregnancy-related diseases, including gestational diabetes mellitus (GDM). The role of NO and its placental targets in GDM pregnancies has yet to be determined. S-Nitrosylation is the NO-derived posttranslational protein modification that can modulate biological functions by forming NO-derived complexes with longer half-life, termed S-nitrosothiol (SNO). Our aim was to examine the presence of endogenous S-nitrosylated proteins in cysteine residues in relation to antioxidant defense, apoptosis, and cellular signal transduction in placental tissue from control (n=8) and GDM (n=8) pregnancies. S-Nitrosylation was measured using the biotin-switch assay, while the expression and protein activity were assessed by immunoblotting and colorimetric methods, respectively. Results indicated that catalase and peroxiredoxin nitrosylation levels were greater in GDM placentas, and that was accompanied by reduced catalase activity. S-Nitrosylation of ERK1/2 and AKT was increased in GDM placentas, and their activities were inhibited. Activities of caspase-3 and caspase-9 were increased, with the latter also showing diminished nitrosylation levels. These findings suggest that S-nitrosylation is a little-known, but critical, mechanism by which NO directly modulates key placental proteins in women with GDM and, as a consequence, maternal and fetal anomalies during pregnancy can occur.
Francisco Visiedo; Celeste Santos-Rosendo; Rosa M. Mateos-Bernal; M. Del Mar Gil-Sánchez; Fernando Bugatto; Manuel Aguilar Diosdado; Carmen Segundo; Cristina López-Tinoco. Characterization of NO-Induced Nitrosative Status in Human Placenta from Pregnant Women with Gestational Diabetes Mellitus. Oxidative Medicine and Cellular Longevity 2017, 2017, 1 -10.
AMA StyleFrancisco Visiedo, Celeste Santos-Rosendo, Rosa M. Mateos-Bernal, M. Del Mar Gil-Sánchez, Fernando Bugatto, Manuel Aguilar Diosdado, Carmen Segundo, Cristina López-Tinoco. Characterization of NO-Induced Nitrosative Status in Human Placenta from Pregnant Women with Gestational Diabetes Mellitus. Oxidative Medicine and Cellular Longevity. 2017; 2017 ():1-10.
Chicago/Turabian StyleFrancisco Visiedo; Celeste Santos-Rosendo; Rosa M. Mateos-Bernal; M. Del Mar Gil-Sánchez; Fernando Bugatto; Manuel Aguilar Diosdado; Carmen Segundo; Cristina López-Tinoco. 2017. "Characterization of NO-Induced Nitrosative Status in Human Placenta from Pregnant Women with Gestational Diabetes Mellitus." Oxidative Medicine and Cellular Longevity 2017, no. : 1-10.
BackgroundGhrelin is a peptide hormone with pleiotropic effects. It stimulates cellular proliferation and inhibits apoptosis-mediated cell death. It prevents diabetes mellitus in several models of pancreas aggression (chemical, surgical and biological toxic insults) in both in vivo and in vitro models, and promotes glucose-stimulated insulin secretion under cytotoxic conditions. It has not yet been tested in vivo in an autoimmune model of diabetes with a persistent insult to the β-cell. Given the immunomodulating effects of ghrelin and its trophic effects on β-cells, we hypothesized that ghrelin treatment during the early stages of insulitis would delay diabetes onset.MethodsBB male rats received ghrelin (10 ng/kg/day) before insulitis development. Glucose metabolism was characterized by glucose and insulin tolerance tests. β-cell mass, islet area, islet number, β-cell clusters, proliferation and apoptosis and degree of insulitis were analyzed by histomorphometry. A Kaplan Meier survival curve was plotted and analyzed applying the Log-Rank (Mantel-Cox) test.ResultsGhrelin treatment significantly reduces the probability of developing diabetes in our model (p < 0.0001). It decreases islet infiltration, and partially prevents β-cell mass loss, enabling the maintenance of β-cell neogenesis and proliferation rates. Furthermore, ghrelin treatment did not induce any metabolic perturbations.ConclusionsThese findings support the hypothesis that ghrelin delays the development of autoimmune diabetes by attenuating insulitis and supporting β-cell mass.General Significance: Ghrelin promotes β-cell viability and function through diverse mechanisms which may have significant implications for diabetes prevention, therapy and also transplant success of both islets and complete pancreas.
Gloria Baena-Nieto; Isabel M. Lomas-Romero; Rosa María Mateos; Noelia Leal-Cosme; Gonzalo Martin Perez-Arana; Manuel Aguilar-Diosdado; Carmen Segundo; Alfonso M. Lechuga-Sancho. Ghrelin mitigatesβ-cell mass loss during insulitis in an animal model of autoimmune diabetes mellitus, the BioBreeding/Worcester rat. Diabetes/Metabolism Research and Reviews 2016, 33, e2813 .
AMA StyleGloria Baena-Nieto, Isabel M. Lomas-Romero, Rosa María Mateos, Noelia Leal-Cosme, Gonzalo Martin Perez-Arana, Manuel Aguilar-Diosdado, Carmen Segundo, Alfonso M. Lechuga-Sancho. Ghrelin mitigatesβ-cell mass loss during insulitis in an animal model of autoimmune diabetes mellitus, the BioBreeding/Worcester rat. Diabetes/Metabolism Research and Reviews. 2016; 33 (1):e2813.
Chicago/Turabian StyleGloria Baena-Nieto; Isabel M. Lomas-Romero; Rosa María Mateos; Noelia Leal-Cosme; Gonzalo Martin Perez-Arana; Manuel Aguilar-Diosdado; Carmen Segundo; Alfonso M. Lechuga-Sancho. 2016. "Ghrelin mitigatesβ-cell mass loss during insulitis in an animal model of autoimmune diabetes mellitus, the BioBreeding/Worcester rat." Diabetes/Metabolism Research and Reviews 33, no. 1: e2813.
Cristina Lopez-Tinoco; Francisco Visiedo; Mar Roca-Rodriguez; Celeste Rosendo; Rosa Mateos; Carmen Segundo; Manuel Aguilar-Diosdado. Oxidative stress in the gestational diabetes mellitus mother and placenta. Endocrine Abstracts 2016, 1 .
AMA StyleCristina Lopez-Tinoco, Francisco Visiedo, Mar Roca-Rodriguez, Celeste Rosendo, Rosa Mateos, Carmen Segundo, Manuel Aguilar-Diosdado. Oxidative stress in the gestational diabetes mellitus mother and placenta. Endocrine Abstracts. 2016; ():1.
Chicago/Turabian StyleCristina Lopez-Tinoco; Francisco Visiedo; Mar Roca-Rodriguez; Celeste Rosendo; Rosa Mateos; Carmen Segundo; Manuel Aguilar-Diosdado. 2016. "Oxidative stress in the gestational diabetes mellitus mother and placenta." Endocrine Abstracts , no. : 1.
Ghrelin is a peptidic hormone, which stimulates cell proliferation and inhibits apoptosis in several tissues, including pancreas. In preclinical stage of type 1 diabetes, proinflammatory cytokines generate a destructive environment for β-cells known as insulitis, which results in loss of β-cell mass and impaired insulin secretion, leading to diabetes. Our aim was to demonstrate that ghrelin could preserve β-cell viability, turnover rate, and insulin secretion acting as a counter balance of cytokines. In the present work we reproduced proinflammatory milieu found in insulitis stage by treating murine cell line INS-1E and rat islets with a cytokine cocktail including IL-1β, IFNγ, and TNFα and/or ghrelin. Several proteins involved in survival pathways (ERK 1/2 and Akt/PKB) and apoptosis (caspases and Bcl-2 protein family and endoplasmic reticulum stress markers) as well as insulin secretion were analyzed. Our results show that ghrelin alone has no remarkable effects on β-cells in basal conditions, but interestingly it activates cell survival pathways, downregulates apoptotic mediators and endoplasmic reticulum stress, and restores insulin secretion in response to glucose when beta-cells are cytokine-exposed. These data suggest a potential role of ghrelin in preventing or slowing down the transition from a preclinical to clinically established diabetes by ameliorating the effects of insulitis on β-cells.
Antonia Diaz Gañete; Gloria Baena-Nieto; Isabel M. Lomas-Romero; José Francisco López-Acosta; Irene Cozar-Castellano; Francisco Medina; Carmen Segundo; Alfonso M. Lechuga-Sancho. Ghrelin's Effects on Proinflammatory Cytokine Mediated Apoptosis and Their Impact on β-Cell Functionality. International Journal of Endocrinology 2015, 2015, 1 -11.
AMA StyleAntonia Diaz Gañete, Gloria Baena-Nieto, Isabel M. Lomas-Romero, José Francisco López-Acosta, Irene Cozar-Castellano, Francisco Medina, Carmen Segundo, Alfonso M. Lechuga-Sancho. Ghrelin's Effects on Proinflammatory Cytokine Mediated Apoptosis and Their Impact on β-Cell Functionality. International Journal of Endocrinology. 2015; 2015 ():1-11.
Chicago/Turabian StyleAntonia Diaz Gañete; Gloria Baena-Nieto; Isabel M. Lomas-Romero; José Francisco López-Acosta; Irene Cozar-Castellano; Francisco Medina; Carmen Segundo; Alfonso M. Lechuga-Sancho. 2015. "Ghrelin's Effects on Proinflammatory Cytokine Mediated Apoptosis and Their Impact on β-Cell Functionality." International Journal of Endocrinology 2015, no. : 1-11.
Cristina Lopez-Tinoco; Francisco Visiedo; Celeste Rosendo; Maria Belen Ojeda; Isabel Mateos; Carmen Segundo; Manuel Aguilar-Diosdado. Role of nitrosative and oxidative stress on the development of gestational diabetes mellitus and their effect in GDM placenta. Endocrine Abstracts 2015, 1 .
AMA StyleCristina Lopez-Tinoco, Francisco Visiedo, Celeste Rosendo, Maria Belen Ojeda, Isabel Mateos, Carmen Segundo, Manuel Aguilar-Diosdado. Role of nitrosative and oxidative stress on the development of gestational diabetes mellitus and their effect in GDM placenta. Endocrine Abstracts. 2015; ():1.
Chicago/Turabian StyleCristina Lopez-Tinoco; Francisco Visiedo; Celeste Rosendo; Maria Belen Ojeda; Isabel Mateos; Carmen Segundo; Manuel Aguilar-Diosdado. 2015. "Role of nitrosative and oxidative stress on the development of gestational diabetes mellitus and their effect in GDM placenta." Endocrine Abstracts , no. : 1.
Cristina Lopez-Tinoco; Francisco Vilchez; Francisco Visiedo; Isabel Mateo; Carmen Segundo; Manuel Aguilar-Diosdado. Paper of oxidative stress and placenta on the development of gestational diabetes mellitus. Endocrine Abstracts 2014, 1 .
AMA StyleCristina Lopez-Tinoco, Francisco Vilchez, Francisco Visiedo, Isabel Mateo, Carmen Segundo, Manuel Aguilar-Diosdado. Paper of oxidative stress and placenta on the development of gestational diabetes mellitus. Endocrine Abstracts. 2014; ():1.
Chicago/Turabian StyleCristina Lopez-Tinoco; Francisco Vilchez; Francisco Visiedo; Isabel Mateo; Carmen Segundo; Manuel Aguilar-Diosdado. 2014. "Paper of oxidative stress and placenta on the development of gestational diabetes mellitus." Endocrine Abstracts , no. : 1.
Nitric oxide (NO) is involved in several biological processes. In type 1 diabetes mellitus (T1DM), proinflammatory cytokines activate an inducible isoform of NOS (iNOS) inβcells, thus increasing NO levels and inducing apoptosis. The aim of the current study is to determine the role of NO (1) in the antiproliferative effect of proinflammatory cytokines IL-1β, IFN-γ, and TNF-αon cultured isletβcells and (2) during the insulitis stage prior to diabetes onset using the Biobreeding (BB) rat strain as T1DM model. Our results indicate that NO donors exert an antiproliferative effect onβcell obtained from cultured pancreatic islets, similar to that induced by proinflammatory cytokines. This cytokine-induced antiproliferative effect can be reversed by L-NMMA, a general NOS inhibitor, and is independent of guanylate cyclase pathway. Assays using NOS isoform specific inhibitors suggest that the NO implicated in the antiproliferative effect of proinflammatory cytokines is produced by inducible NOS, although not in an exclusive way. In BB rats, early treatment with L-NMMA improves the initial stage of insulitis. We conclude that NO is an important mediator of antiproliferative effect induced by proinflammatory cytokines on culturedβcell and is implicated inβ-cell proliferation impairment observed early from initial stage of insulitis.
Laura Quintana-Lopez; Manuel Blandino-Rosano; Gonzalo Martin Perez-Arana; Alberto Cebada-Aleu; Alfonso Lechuga-Sancho; Manuel Aguilar Diosdado; Carmen Segundo. Nitric Oxide Is a Mediator of Antiproliferative Effects Induced by Proinflammatory Cytokines on Pancreatic Beta Cells. Mediators of Inflammation 2013, 2013, 1 -10.
AMA StyleLaura Quintana-Lopez, Manuel Blandino-Rosano, Gonzalo Martin Perez-Arana, Alberto Cebada-Aleu, Alfonso Lechuga-Sancho, Manuel Aguilar Diosdado, Carmen Segundo. Nitric Oxide Is a Mediator of Antiproliferative Effects Induced by Proinflammatory Cytokines on Pancreatic Beta Cells. Mediators of Inflammation. 2013; 2013 ():1-10.
Chicago/Turabian StyleLaura Quintana-Lopez; Manuel Blandino-Rosano; Gonzalo Martin Perez-Arana; Alberto Cebada-Aleu; Alfonso Lechuga-Sancho; Manuel Aguilar Diosdado; Carmen Segundo. 2013. "Nitric Oxide Is a Mediator of Antiproliferative Effects Induced by Proinflammatory Cytokines on Pancreatic Beta Cells." Mediators of Inflammation 2013, no. : 1-10.
The relationship between late-onset gestational diabetes mellitus [GDM] and oxidative stress is not well known, and the importance of the oxidant/antioxidant equilibrium in the clinical evolution and its complications require elucidation. The aim of the study was to evaluate the relationships between maternal levels of markers of oxidative stress in women with late-onset GDM that, potentially, may have considerable clinical implications in the pathogenesis and/or the evolution of GDM. Pregnant women (n = 78; 53 with GDM, 25 controls), between the 24th and 29th week of gestation, were enrolled. Both groups were analysed for demographic data, perinatal and obstetrics outcomes together with the levels of the marker's oxidative stress and antioxidant status. Control versus patient results in the univariate analysis were the following: pre-gestational body mass index [BMI] 23.31 ± 4.2 vs. 27.13 ± 4.6 kg/m(2) (P = 0.001); weeks at delivery 39.2 ± 3.05 vs. 38.9 ± 1.8 (P = 0.09); Caesarean delivery 12.5 vs. 43% (P = 0.004); macrosomia 4 vs. 9.4% (P = 0.6); lipoperoxides [LPO] 2.06 ± 1.00 vs. 3.14 ± 1.55 μmol/mg (P = 0.001); catalase 3.23 ± 1.41 vs. 2.52 ± 1.3 nmol/min/ml (P = 0.03); superoxide dismutase [SOD] 0.11 ± 0.04 vs. 0.08 ± 0.01 U/ml (P = 0.0003); glutathione peroxidase [GPX] 0.03 ± 0.006 vs. 0.025 ± 0.006 nmol/min/ml (P = 0.01); glutathione reductase [GSH] 0.004 ± 0.002 vs. 0.004 ± 0.004 nmol/min/ml (P = 0.9)]; and glutathione transferase [GST] 0.0025 ± 0.0012 vs. 0.0027 ± 0.00017 nmol/min/ml (P = 0.7). Multivariate analysis showed catalase might have a protective effect against GDM development and LPO seems to be a risk factor for the disease. These data suggest an increase in oxidative stress and a decrease in antioxidative defence in women with late-onset GDM and, as such, may have considerable clinical implications in the pathogenesis and/or the course of the pregnancy in these patients.
Cristina López-Tinoco; Mar Roca; Amor García-Valero; Mora Murri; Francisco J. Tinahones; Carmen Segundo; José L. Bartha; Manuel Aguilar-Diosdado. Oxidative stress and antioxidant status in patients with late-onset gestational diabetes mellitus. Acta Diabetologica 2011, 50, 201 -208.
AMA StyleCristina López-Tinoco, Mar Roca, Amor García-Valero, Mora Murri, Francisco J. Tinahones, Carmen Segundo, José L. Bartha, Manuel Aguilar-Diosdado. Oxidative stress and antioxidant status in patients with late-onset gestational diabetes mellitus. Acta Diabetologica. 2011; 50 (2):201-208.
Chicago/Turabian StyleCristina López-Tinoco; Mar Roca; Amor García-Valero; Mora Murri; Francisco J. Tinahones; Carmen Segundo; José L. Bartha; Manuel Aguilar-Diosdado. 2011. "Oxidative stress and antioxidant status in patients with late-onset gestational diabetes mellitus." Acta Diabetologica 50, no. 2: 201-208.
In autoimmune type 1 diabetes mellitus, proinflammatory cytokine-mediated apoptosis of β-cells has been considered to be the first event directly responsible for β-cell mass reduction. In the Bio-Breeding (BB) rat, an in vivo model used in the study of autoimmune diabetes, β-cell apoptosis is observed from 9 wk of age and takes place after an insulitis period that begins at an earlier age. Previous studies by our group have shown an antiproliferative effect of proinflammatory cytokines on cultured β-cells in Wistar rats, an effect that was partially reversed by Exendin-4, an analogue of glucagon-like peptide-1. In the current study, the changes in β-cell apoptosis and proliferation during insulitis stage were also determined in pancreatic tissue sections in normal and thymectomized BB rats, as well as in Wistar rats of 5, 7, 9, and 11 wk of age. Although stable β-cell proliferation in Wistar and thymectomized BB rats was observed along the course of the study, a decrease in β-cell proliferation and β-cell mass from the age of 5 wk, and prior to the commencement of apoptosis, was noted in BB rats. Exendin-4, in combination with anti-interferon-γ antibody, induced a near-total recovery of β-cell proliferation during the initial stages of insulitis. This highlights the importance of early intervention and, as well, the possibilities of new therapeutic approaches in preventing autoimmune diabetes by acting, initially, in the insulitis stage and, subsequently, on β-cell regeneration and on β-cell apoptosis.
Gonzalo Martin Perez-Arana; Manuel Blandino-Rosano; José Arturo Prada-Oliveira; Manuel Aguilar Diosdado; Carmen Segundo. Decrease in β-Cell Proliferation Precedes Apoptosis during Diabetes Development in Bio-Breeding/Worcester Rat: Beneficial Role of Exendin-4. Endocrinology 2010, 151, 2538 -2546.
AMA StyleGonzalo Martin Perez-Arana, Manuel Blandino-Rosano, José Arturo Prada-Oliveira, Manuel Aguilar Diosdado, Carmen Segundo. Decrease in β-Cell Proliferation Precedes Apoptosis during Diabetes Development in Bio-Breeding/Worcester Rat: Beneficial Role of Exendin-4. Endocrinology. 2010; 151 (6):2538-2546.
Chicago/Turabian StyleGonzalo Martin Perez-Arana; Manuel Blandino-Rosano; José Arturo Prada-Oliveira; Manuel Aguilar Diosdado; Carmen Segundo. 2010. "Decrease in β-Cell Proliferation Precedes Apoptosis during Diabetes Development in Bio-Breeding/Worcester Rat: Beneficial Role of Exendin-4." Endocrinology 151, no. 6: 2538-2546.
Pancreatic β-cell homeostasis is a balance between programmed cell death (apoptosis) and regeneration. Although autoimmune diabetes mellitus type 1 (DM1) is the most-studied cause of β-cell mass loss by pro-inflammatory cytokine-induced apoptosis, influences of a pro-inflammatory environment on β-cell regenerative response have been poorly studied. In this study, we assess the anti-proliferative effect of pro-inflammatory cytokines and glucose concentration on rat pancreatic β cells and the potential protective role of glucagon-like peptide (GLP-1). Apoptotic and proliferating islet cells were stained using the DeadEnd Fluorimetric TUNEL System and 5-bromo-2′-deoxyuridine label respectively, in the presence–absence of varying concentrations of glucose, pro-inflammatory cytokines, and GLP-1. The potential signaling pathways involved were evaluated by western blot. Considerable anti-proliferative effects of pro-inflammatory cytokines interleukin (IL)-1β, interferon (IFN)-γ, and tumour necrosis factor-α (TNF-α) were observed. The effects were synergistic and independent of glucose concentration, and appeared to be mediated by the inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) activation, the signaling pathway involved in β-cell replication. GLP-1 completely reversed the cytokine-induced inhibition of ERK phosphorylation and increased β-cell proliferation threefold in cytokine-treated cultures. While pro-inflammatory cytokines reduced islet cell ERK1/2 activation and β-cell proliferation in pancreatic islet culture, GLP-1 was capable of reversing this effect. These data suggest a possible pharmacological application of GLP-1 in the treatment of early stage DM1, to prevent the loss of pancreatic β cells as well as to delay the development of overt diabetes.
M Blandino-Rosano; G Perez-Arana; J M Mellado-Gil; C Segundo; M Aguilar-Diosdado. Anti-proliferative effect of pro-inflammatory cytokines in cultured β cells is associated with extracellular signal-regulated kinase 1/2 pathway inhibition: protective role of glucagon-like peptide -1. Journal of Molecular Endocrinology 2008, 41, 35 -44.
AMA StyleM Blandino-Rosano, G Perez-Arana, J M Mellado-Gil, C Segundo, M Aguilar-Diosdado. Anti-proliferative effect of pro-inflammatory cytokines in cultured β cells is associated with extracellular signal-regulated kinase 1/2 pathway inhibition: protective role of glucagon-like peptide -1. Journal of Molecular Endocrinology. 2008; 41 (1):35-44.
Chicago/Turabian StyleM Blandino-Rosano; G Perez-Arana; J M Mellado-Gil; C Segundo; M Aguilar-Diosdado. 2008. "Anti-proliferative effect of pro-inflammatory cytokines in cultured β cells is associated with extracellular signal-regulated kinase 1/2 pathway inhibition: protective role of glucagon-like peptide -1." Journal of Molecular Endocrinology 41, no. 1: 35-44.
Human plasma cells (PC) are present in cell suspensions obtained from the tonsil by mechanical disaggregation (PCMECH). The present study shows that a collagenase treatment of tonsillar debris remaining after mechanical disaggregation yielded similar proportions of PC (PCCOLL). Moreover, PCMECH were present in suspensions highly enriched in germinal center cells whereas PCCOLL contained most of the IgA-secreting cells, suggesting their predominant location in follicular and parafollicular areas and connective tissue-rich zones such as tonsil subepithelium, respectively. Tonsil PCMECH and PCCOLL shared the phenotype CD38high CD19+ CD20low CD45high, expressed equivalent amounts of PRDI BF1/Blimp-1 transcription factor, and carried similarly mutated IgVH6 genes. However, they differed in several features. 1) PCMECH still expressed the early B cell transcription factor BSAP and were HLA-DRhigh; in contrast, PCCOLL were BSAP−and HLA-DRlow. 2) PCMECH were CD95+ and Bcl-2+/− whereas PCCOLL showed CD95+/− and Bcl-2+ expression; in addition, PCMECH exhibited increased spontaneous apoptosis. 3) The two PC subsets exhibited distinctive adhesion molecule profiles, since PCCOLL expressed higher levels of CD31, CD44, and CD49d, but a lower level of CD11a than PCMECH. These results suggest that PCMECH are recently generated, short-living PC, and PCCOLL constitutes a subset with higher maturity and survival, which resides in connective tissue-rich areas.
Francisco Medina; Carmen Segundo; Gema Jiménez-Gómez; Inés González-García; Antonio Campos-Caro; José A. Brieva. Higher maturity and connective tissue association distinguish resident from recently generated human tonsil plasma cells. Journal of Leukocyte Biology 2007, 82, 1430 -1436.
AMA StyleFrancisco Medina, Carmen Segundo, Gema Jiménez-Gómez, Inés González-García, Antonio Campos-Caro, José A. Brieva. Higher maturity and connective tissue association distinguish resident from recently generated human tonsil plasma cells. Journal of Leukocyte Biology. 2007; 82 (6):1430-1436.
Chicago/Turabian StyleFrancisco Medina; Carmen Segundo; Gema Jiménez-Gómez; Inés González-García; Antonio Campos-Caro; José A. Brieva. 2007. "Higher maturity and connective tissue association distinguish resident from recently generated human tonsil plasma cells." Journal of Leukocyte Biology 82, no. 6: 1430-1436.
Thyroid-infiltrating B (Thyr-B) lymphocytes are thought to play an important role in the pathogenic mechanisms underlying Graves' disease. In this study, a broad phenotypic analysis of these cells has been performed in 15 consecutive patients who underwent thyroidectomy. Data reveal the occurrence of two distinct types of Thyr-B cell infiltrates. Type 1 was present in most of the cases (10/15) and consisted of a combination of IgM+ IgD(low to-) B lymphocytes showing features of marginal zone B cells, and IgG+ classic memory B cells. In contrast, in 5 of the 15 cases, a second type of Thyr-B cell infiltrate occurred, exhibiting the profile IgM- IgD- CD44(low to-) CD38++ CD71+ CD95+. This phenotype is highly suggestive of germinal center (GC) B cells, a finding not always anticipated from routine histologic examination. The presence of these ectopic GC was closely associated with the elevated serum level of anti-thyroid peroxidase (TPO), but not with anti-thyrotropin receptor (TSHR), autoantibodies. Moreover, local active anti-thyroglobulin (Tg) antibody secretion was only detected in cultures of type 2 Thyr-B cells. These findings indicate that high titers of anti-TPO, but not anti-TSHR antibody, might be associated with intrathyroidal GC development.
Carmen Segundo; Carmen Rodríguez; Manuel Aguilar; Antonio García-Poley; Inmaculada Gavilán; Carmen Bellas; José A. Brieva. Differences in Thyroid-Infiltrating B Lymphocytes in Patients with Graves' Disease: Relationship to Autoantibody Detection. Thyroid 2004, 14, 337 -344.
AMA StyleCarmen Segundo, Carmen Rodríguez, Manuel Aguilar, Antonio García-Poley, Inmaculada Gavilán, Carmen Bellas, José A. Brieva. Differences in Thyroid-Infiltrating B Lymphocytes in Patients with Graves' Disease: Relationship to Autoantibody Detection. Thyroid. 2004; 14 (5):337-344.
Chicago/Turabian StyleCarmen Segundo; Carmen Rodríguez; Manuel Aguilar; Antonio García-Poley; Inmaculada Gavilán; Carmen Bellas; José A. Brieva. 2004. "Differences in Thyroid-Infiltrating B Lymphocytes in Patients with Graves' Disease: Relationship to Autoantibody Detection." Thyroid 14, no. 5: 337-344.
Background and aims: Large numbers of plasma cells (PC) localise in the intestinal lamina propria (LP) where they play a critical role in the defence against pathogens. This study analyses the level of maturation reached by normal human colon LPPC in comparison with that of bone marrow (BM) PC. Methods: A technique was designed to purify LPPC by combining collagenase digestion of the mucosal layer and immunomagnetic selection of CD54+ LP cells. It provided highly purified PC, as demonstrated by morphology, CD38h phenotype, and cytoplasmic IgA staining criteria. This procedure allowed comparison of in vitro functional capacities and a broad phenotypic analysis of BMPC and LPPC. Results: LPPC and BMPC exhibited identical expression of differentiation markers (CD19−/+, CD20−, HLA-DRlow/−, VS38chigh), survival molecules (CD95 low/−, Bcl-2+), and B cell transcription factor profile, as well as similar in vitro Ig secreting kinetics (14 days) and lack of susceptibility to apoptosis by CD95 ligation. In contrast, they markedly differed in adhesion molecule expression, as LPPC showed higher levels of CD44 and CD21 and were α4β7+ whereas BMPC lacked this integrin and expressed higher levels of CD49d and CD31. Conclusion: These data indicate that PC at effector sites of the humoral response (BM and LP) show similar high differentiation, survival, and functional features but display a distinctive pattern of adhesion molecules, probably related to their respective homing locations.
F Medina; Carmen Segundo; Antonio Campos-Caro; I Salcedo; A García-Poley; J A Brieva. Isolation, maturational level, and functional capacity of human colon lamina propria plasma cells. Gut 2003, 52, 383 -389.
AMA StyleF Medina, Carmen Segundo, Antonio Campos-Caro, I Salcedo, A García-Poley, J A Brieva. Isolation, maturational level, and functional capacity of human colon lamina propria plasma cells. Gut. 2003; 52 (3):383-389.
Chicago/Turabian StyleF Medina; Carmen Segundo; Antonio Campos-Caro; I Salcedo; A García-Poley; J A Brieva. 2003. "Isolation, maturational level, and functional capacity of human colon lamina propria plasma cells." Gut 52, no. 3: 383-389.
Neuronal cell death is a genuine developmental process, with precise regulation and defined roles. In striking contrast, characterization of cell death that occurs at early stages of neural development is very limited. We previously showed that embryonic proinsulin increases the level of the chaperone heat shock cognate 70 (Hsc70) and reduces the incidence of apoptosis in the neurulating chick embryo [de la Rosa, et al. (1998), Proc. Natl. Acad. Sci. USA, 95, 9950]. We now demonstrate that Hsc70 is directly involved in cell survival during neurulation, as specific downregulation of endogenous Hsc70 by antisense oligodeoxynucleotide interference provoked an increase in apoptosis both in vitro and in ovo. In parallel, activation of caspase-3 was increased after hsc70 antisense oligodeoxynucleotide treatment. Dead cells were located mostly in the developing nervous system, distributed in areas where the incidence of cell death was high. These areas coincided both in vivo and under different death-inducing conditions, including antisense interference and growth factor deprivation. Hsc70 immunostaining was strong in at least some areas of high cell death. Apoptotic cells within these areas presented undetectable Hsc70 levels, however, suggesting that this protein acts as an intrinsic protector of neuroepithelial and neural precursor cells.
Eva Rubio; Ana I. Valenciano; Carmen Segundo; Noelia Sánchez; Flora De Pablo; Enrique J. De La Rosa. Programmed cell death in the neurulating embryo is prevented by the chaperone heat shock cognate 70. European Journal of Neuroscience 2002, 15, 1646 -1654.
AMA StyleEva Rubio, Ana I. Valenciano, Carmen Segundo, Noelia Sánchez, Flora De Pablo, Enrique J. De La Rosa. Programmed cell death in the neurulating embryo is prevented by the chaperone heat shock cognate 70. European Journal of Neuroscience. 2002; 15 (10):1646-1654.
Chicago/Turabian StyleEva Rubio; Ana I. Valenciano; Carmen Segundo; Noelia Sánchez; Flora De Pablo; Enrique J. De La Rosa. 2002. "Programmed cell death in the neurulating embryo is prevented by the chaperone heat shock cognate 70." European Journal of Neuroscience 15, no. 10: 1646-1654.