Research Center Biomedica En Red Of Diabetes
Research Center Biomedica En Red Of Diabetes
Bartolome A.,Complutense University of Madrid |
Bartolome A.,Research Center Biomedica En Red Of Diabetes |
Bartolome A.,Institute Investigacion Sanitaria Del Hospital Clinico San Carlos Of Madrid Idissc |
Guillen C.,Complutense University of Madrid |
And 2 more authors.
Vitamins and Hormones | Year: 2014
Exquisite regulation of insulin secretion by pancreatic β-cells is essential to maintain metabolic homeostasis. β-Cell mass must be accordingly adapted to metabolic needs and can be largely modified under different situations. The mammalian target of rapamycin (mTOR) complexes has been consistently identified as key modulators of β-cell mass. mTOR can be found into two different complexes, mTORC1 and mTORC2. Under systemic insulin resistance, mTORC1/mTORC2 signaling in β-cells is needed to increase β-cell mass and insulin secretion. However, type 2 diabetes arises when these compensatory mechanisms fail, being the role of mTOR complexes still obscure in β-cell failure. In this chapter, we introduce the protein composition and regulation of mTOR complexes and their role in pancreatic β-cells. Furthermore, we describe their main signaling effectors through the review of numerous animal models, which indicate the essential role of mTORC1/mTORC2 in pancreatic β-cell mass regulation. © 2014 Elsevier Inc.
Sanz C.,Complutense University of Madrid |
Sanz C.,Research Center Biomedica En Red Of Diabetes |
Blazquez E.,Complutense University of Madrid |
Blazquez E.,Research Center Biomedica En Red Of Diabetes
American Journal of Physiology - Endocrinology and Metabolism | Year: 2011
In humans, glucagon-like peptide (GLP-1) functions during adult life as an incretin hormone with anorexigenic and antidiabetogenic properties. Also, the therapeutic potential of GLP-1 in preventing the adipocyte hyperplasia associated with obesity and in bolstering the maintenance of human mesenchymal stem cell (hMSC) stores by promoting the proliferation and cytoprotection of hMSC seems to be relevant. Since these observations suggest a role for GLP-1 during developmental processes, the aim of the present work was to characterize GLP-1 in early development as well as its gene targets in mouse embryonic stem (mES) cells. Mouse embryos E6, E8, and E10.5 and pluripotent mES were used for the inmunodetection of GLP-1 and GLP-1 receptor. Quantitative real-time PCR was used to determine the expression levels of GLP-1R in several tissues from E12.5 mouse embryos. Additionally, GLP-1 gene targets were studied in mES by multiple gene expression analyses. GLP-1 and its receptors were identified in mES and during embryonic development. In pluripotent mES, GLP-1 modified the expression of endodermal, ectodermal, and mesodermal gene markers as well as sonic hedgehog, noggin, members of the fibroblast and hepatic growth factor families, and others involved in pancreatic development. Additionally, GLP-1 promoted the expression of the antiapoptotic gene bcl2 and at the same time reduced proapoptotic caspase genes. Our results indicate that apart from the effects and therapeutic benefits of GLP-1 in adulthood, it may have additional gene targets in mES cells during embryonic life. Furthermore, the pathophysiological implications of GLP-1 imbalance in adulthood may have a counterpart during development. © 2011 the American Physiological Society.
Testa R.,INRCA IRCCS National Institute |
Genovese S.,IRCCS Gruppo Multimedica |
Ceriello A.,Insititut dInvestigacions Biomediques August Pi i Sunyer IDIBAPS |
Ceriello A.,Research Center Biomedica En Red Of Diabetes
Current Opinion in Clinical Nutrition and Metabolic Care | Year: 2014
Quality of nutrition plays a central role in illnesses such as diabetes and its complications. Dietary and lifestyle habits may have a strong impact, either worsening or improving the evolution of diabetes mellitus. Some factors, such as obesity, worsen the illness, causing chronic inflammation, lipid metabolic disorder, accelerated atherosclerosis, increased risk for thrombosis, hypertension, hyperinsulinemia, insulin resistance, and cellular senescence. Some other nutritional components, however, have an opposite effect, probably increasing antioxidant defense. RECENT FINDINGS: The effects of nutritional factors on cellular senescence in diabetic patients are described in this review. In particular, we discuss some of the nutritional causes of cellular senescence in diabetes mellitus and focus on different nutraceutical compounds that can affect cellular senescence. Furthermore, relevant mechanisms of action are also described. SUMMARY: Diet and nutraceutical factors have important effects on diabetes mellitus. Some molecules, which improve antioxidant defense, may counteract cellular senescence. A good lifestyle with physical activity and good weight control can improve the quality of life in diabetic people; on the contrary, obesity and vitamin deficiencies may worsen the evolution of this illness, even inducing cellular senescence.Copyright © Lippincott Williams &Wilkins.
Hale L.J.,University of Bristol |
Hurcombe J.,University of Bristol |
Lay A.,University of Bristol |
Santamaria B.,Institute Investigaciones Biomedicas Alberto Sols |
And 7 more authors.
American Journal of Physiology - Renal Physiology | Year: 2013
Podocytes are critically important for maintaining the integrity of the glomerular filtration barrier and preventing albuminuria. Recently, it has become clear that to achieve this, they need to be insulin sensitive and produce an optimal amount of VEGF-A. In other tissues, insulin has been shown to regulate VEGF-A release, but this has not been previously examined in the podocyte. Using in vitro and in vivo approaches, in the present study, we now show that insulin regulates VEGF-A in the podocyte in both mice and humans via the insulin receptor (IR). Insulin directly increased VEGF-A mRNA levels and protein production in conditionally immortalized wild-type human and murine podocytes. Furthermore, when podocytes were rendered insulin resistant in vitro (using stable short hairpin RNA knockdown of the IR) or in vivo (using transgenic podocyte-specific IR knockout mice), podocyte VEGF-A production was impaired. Importantly, in vivo, this occurs before the development of any podocyte damage due to podocyte insulin resistance. Modulation of VEGF-A by insulin in the podocyte may be another important factor in the development of glomerular disease associated with conditions in which insulin signaling to the podocyte is deranged. © 2013 the American Physiological Society.
Balgoma D.,Institute Biologia y Genetica Molecular |
Balgoma D.,Research Center Biomedica En Red Of Diabetes |
Montero O.,Institute Biologia y Genetica Molecular |
Montero O.,Research Center Biomedica En Red Of Diabetes |
And 4 more authors.
Biochimie | Year: 2010
The distribution of fatty acids among cellular glycerophospholipids is finely regulated by the CoA-dependent acylation of lysophospholipids followed by transacylation reactions. Arachidonic acid is the fatty acid precursor of a wide family of bioactive compounds called the eicosanoids, with key roles in innate immunity and inflammation. Because availability of free AA constitutes a rate-limiting step in the generation of eicosanoids by mammalian cells, many studies have been devoted to characterize the processes of arachidonate liberation from phospholipids by phospholipase A2s and its re-incorporation and further remodeling back into phospholipids by acyltransferases and transacylases. These studies have traditionally been conducted by using radioactive precursors which do not allow the identification of the phospholipid molecular species involved in these processes. Nowadays, lipidomic approaches utilizing mass spectrometry provide a new frame for the analysis of unique phospholipid species involved in fatty acid release and phospholipid incorporation and remodeling. This review focuses on the mass spectrometry techniques applied to the study of phospholipid fatty acid trafficking and the recent advances that have been achieved by the use of this technique. © 2009.
Duran J.,Barcelona Institute for Research in Biomedicine |
Duran J.,Research Center Biomedica En Red Of Diabetes |
Gruart A.,Pablo De Olavide University |
Garcia-Rocha M.,Barcelona Institute for Research in Biomedicine |
And 4 more authors.
Human Molecular Genetics | Year: 2014
Lafora disease is a fatal neurodegenerative condition characterized by the accumulation of abnormal glycogen inclusions known as Lafora bodies. It is an autosomal recessive disorder caused by mutations in either the laforin or malin gene. To study whether glycogen is primarily responsible for the neurodegeneration in Lafora disease, we generated malin knockout mice with impaired (totally or partially) glycogen synthesis. These animals did not show the increase in markers of neurodegeneration, the impairments in electrophysiological properties of hippocampal synapses, nor the susceptibility to kainate-induced epilepsy seen in the malin knockout model. Interestingly, the autophagy impairment that has beendescribedinmalin knockout animalswasalso rescued in this double knockout model. Conversely, two other mouse models in which glycogen is over-accumulated in the brain independently of the lack of malin showed impairment in autophagy. Our findings reveal that glycogen accumulation accounts for the neurodegeneration and functional consequences seen in the malin knockout model, as well as the impaired autophagy. These results identify the regulation of glycogen synthesis as a key target for the treatment of Lafora disease. © The Author 2014. Published by Oxford University Press. All rights reserved.
Schneeberger M.,Institute dInvestigacions Biomediques August Pi i Sunyer IDIBAPS |
Schneeberger M.,University of Barcelona |
Schneeberger M.,Research Center Biomedica En Red Of Diabetes |
Gomis R.,Institute dInvestigacions Biomediques August Pi i Sunyer IDIBAPS |
And 4 more authors.
Journal of Endocrinology | Year: 2014
Alterations in adequate energy balance maintenance result in serious metabolic disturbances such as obesity. In mammals, this complex process is orchestrated by multiple and distributed neuronal circuits. Hypothalamic and brainstem neuronal circuits are critically involved in the sensing of circulating and local factors conveying information about the energy status of the organism. The integration of these signals culminates in the generation of specific and coordinated physiological responses aimed at regulating energy balance through the modulation of appetite and energy expenditure. In this article, we review current knowledge on the homeostatic regulation of energy balance, emphasizing recent advances in mouse genetics, electrophysiology, and optogenetic techniques that have greatly contributed to improving our understanding of this central process. © 2014 Society for Endocrinology.
Marroqui L.,Research Center Biomedica En Red Of Diabetes |
Marroqui L.,University Miguel Hernández |
Gonzalez A.,Research Center Biomedica En Red Of Diabetes |
Gonzalez A.,University Miguel Hernández |
And 12 more authors.
Journal of Molecular Endocrinology | Year: 2012
Leptin plays an important role in the control of food intake, energy expenditure, metabolism, and body weight. This hormone also has a key function in the regulation of glucose homeostasis. Although leptin acts through central and peripheral mechanisms to modulate glucose metabolism, the pancreatic b-cell of the endocrine pancreas is a critical target of leptin actions. Leptin receptors are present in the b-cell, and their activation directly inhibits insulin secretion from these endocrine cells. The effects of leptin on insulin occur also in the long term, since this hormone inhibits insulin gene expression as well. Additionally, b-cell mass can be affected by leptin through changes in proliferation, apoptosis, or cell size. All these different functions in the b-cell are triggered by leptin as a result of the large diversity of signaling pathways that this hormone is able to activate in the endocrine pancreas. Therefore, leptin can participate in glucose homeostasis owing to different levels of modulation of the pancreatic b-cell population. Furthermore, it has been proposed that alterations in this level of regulation could contribute to the impairment of β-cell function in obesity states. In the present review, we will discuss all these issues with special emphasis on the effects and pathways of leptin signaling in the pancreatic β-cell. © 2012 Society for Endocrinology.
Martin M.A.,Institute Ciencia Y Tecnologia Of Alimentos Y Nutricion Ictan Csic |
Martin M.A.,Research Center Biomedica En Red Of Diabetes |
Ramos S.,Institute Ciencia Y Tecnologia Of Alimentos Y Nutricion Ictan Csic |
Cordero-Herrero I.,Institute Ciencia Y Tecnologia Of Alimentos Y Nutricion Ictan Csic |
And 2 more authors.
Nutrients | Year: 2013
Diabetes mellitus is associated with reductions in glutathione, supporting the critical role of oxidative stress in its pathogenesis. Antioxidant food components such as flavonoids have a protective role against oxidative stress-induced degenerative and age-related diseases. Flavonoids constitute an important part of the human diet; they can be found in most plant foods, including green tea, grapes or cocoa and possess multiple biological activities. This study investigates the chemo-protective effect of a cocoa phenolic extract (CPE) containing mainly flavonoids against oxidative stress induced by tert-butylhydroperoxide (t-BOOH) on Ins-1E pancreatic beta cells. Cell viability and oxidative status were evaluated. Ins-1E cells treatment with 5-20 μg/mL CPE for 20 h evoked no cell damage and did not alter ROS production. Addition of 50 μM t-BOOH for 2 h increased ROS and carbonyl groups content and decreased reduced glutathione level. Pre-treatment of cells with CPE significantly prevented the t-BOOH-induced ROS and carbonyl groups and returned antioxidant defences to adequate levels. Thus, Ins-1E cells treated with CPE showed a remarkable recovery of cell viability damaged by t-BOOH, indicating that integrity of surviving machineries in the CPE-treated cells was notably protected against the oxidative insult. © 2013 by the authors; licensee MDPI, Basel, Switzerland.
Cordero-Herrera I.,Institute of Food Science and Technology and Nutrition ICTAN |
Martin M.A.,Institute of Food Science and Technology and Nutrition ICTAN |
Martin M.A.,Research Center Biomedica En Red Of Diabetes |
Goya L.,Institute of Food Science and Technology and Nutrition ICTAN |
Ramos S.,Institute of Food Science and Technology and Nutrition ICTAN
Molecular Nutrition and Food Research | Year: 2015
Scope: Oxidative stress plays a main role in the pathogenesis of type 2 diabetes mellitus. Cocoa and (-)-epicatechin (EC), a main cocoa flavanol, have been suggested to exert beneficial effects in type 2 diabetes mellitus because of their protective effects against oxidative stress and insulin-like properties. In this study, the protective effect of EC and a cocoa phenolic extract (CPE) against oxidative stress induced by a high-glucose challenge, which causes insulin resistance, was investigated on hepatic HepG2 cells. Methods and results: Oxidative status, phosphorylated mitogen-activated protein kinases (MAPKs), nuclear factor E2 related factor 2 (Nrf2) and p-(Ser)-IRS-1 expression, and glucose uptake were evaluated. EC and CPE regulated antioxidant enzymes and activated extracellular-regulated kinase and Nrf2. EC and CPE pre-treatment prevented high-glucose-induced antioxidant defences and p-MAPKs, and maintained Nrf2 stimulation. The presence of selective MAPK inhibitors induced changes in redox status, glucose uptake, p-(Ser)- and total IRS-1 levels that were observed in CPE-mediated protection. Conclusion: EC and CPE recovered redox status of insulin-resistant HepG2 cells, suggesting that the functionality in EC- and CPE-treated cells was protected against high-glucose-induced oxidative insult. CPE beneficial effects on redox balance and insulin resistance were mediated by targeting MAPKs. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.