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INTRODUCTION: Cutaneous myeloid sarcoma is a rare extramedullary tumour of immature myeloid cells. It is most often associated with acute myeloid leukaemia, and more rarely with myelodysplastic/myeloproliferative disease. PATIENTS AND METHODS: Herein we report a case of cutaneous myeloid sarcoma associated with myelodysplastic/myeloproliferative disease in an 84-year-old man with a diffuse purple papular and nodular rash. The disease course was marked by a spontaneous and total regression for two months. Given the patient's age and general condition, chemotherapy could not be given. DISCUSSION: Cutaneous myeloid sarcoma is rare. It is often associated with acute myeloid leukaemia, and more rarely with myelodysplastic/myeloproliferative disease, but it can occur in isolation. Diagnosis is particularly difficult and is based a consistent body of clinical and histological evidence. Spontaneous regression is very rare and involves immunological mechanisms that are still incompletely understood. Recurrence occurs within a variable time frame and is often associated with transformation to acute myeloid leukaemia if this was not already present at the time of diagnosis. CONCLUSION: Herein we report an extremely rare case of spontaneous regression of cutaneous myeloid sarcoma associated with myelodysplastic/myeloproliferative disease.
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Sarcoma Mieloide , Neoplasias Cutáneas , Anciano de 80 o más Años , Humanos , Masculino , Recurrencia Local de Neoplasia , Remisión Espontánea , Sarcoma Mieloide/diagnóstico , Sarcoma Mieloide/tratamiento farmacológico , Piel , Neoplasias Cutáneas/tratamiento farmacológicoRESUMEN
PURPOSE: The aim of this study was to test the effect of intrapersonal and interpersonal emotional competence on cancer patients' supportive care needs, as mediated by anxiety and depression symptoms. METHODS: Cross-sectional design: 137 cancer patients (42% breast or ovarian cancer, 58% gastrointestinal cancer) in 4 French hospitals completed the Profile of Emotional Competence (PEC), the Hospital Anxiety and Depression Scale (HADS), and the Supportive Care Needs Survey Short Form (SCNS-SF). Bootstrap methods with PROCESS Macro were used to test multiple mediation models. RESULTS: Emotional competence presented a direct or indirect beneficial effect on the satisfaction of supportive care needs, anxiety and depression symptoms. As expected, anxiety and depression symptoms had also strong positive correlations with unmet needs. All multiple mediation models were significant, except for physical needs: intrapersonal and interpersonal emotional competence impacted anxiety and depression symptoms, which in turn impacted psychological, sexual, care/support, and information needs. CONCLUSIONS: These innovative results show the important effect of patients' emotional competence on their supportive care need satisfaction, as mediated by anxiety and depression. Consequently, patients with high emotional competence may require less psychosocial input from medical clinicians. Thus, emotional competence may be integrated into health models and psychosocial interventions to improve patient adjustment. Further investigation is, however, needed to know which are the most beneficial specific emotional competences and at what point of the cancer pathway.
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Ansiedad/psicología , Depresión/psicología , Emociones/fisiología , Evaluación de Necesidades/normas , Negociación/métodos , Neoplasias/psicología , Apoyo Social , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Neoplasias/patología , Encuestas y CuestionariosRESUMEN
Upon in vitro induction or in vivo implantation, the stem cells of the dental pulp display hallmarks of odontoblastic, osteogenic, adipogenic or neuronal cells. However, whether these phenotypes result from genuine multipotent cells or from coexistence of distinct progenitors is still an open question. Furthermore, determining whether a single cell-derived progenitor is capable of undergoing a differentiation cascade leading to tissue repair in situ is important for the development of cell therapy strategies. Three clonal pulp precursor cell lines (A4, C5, H8), established from embryonic ED18 first molars of mouse transgenic for a recombinant plasmid adeno-SV40, were induced to differentiate towards the odonto/osteogenic, chondrogenic or adipogenic programme. Expression of phenotypic markers of each lineage was evaluated by RT-PCR, histochemistry or immunocytochemistry. The clones were implanted into mandibular incisors or calvaria of adult mice. The A4 clone was capable of being recruited towards at least 3 mesodermal lineages in vitro and of contributing to dentin-like or bone formation, in vivo, thus behaving as a multipotent cell. In contrast, the C5 and H8 clones displayed a more restricted potential. Flow cytometric analysis revealed that isolated monopotent and multipotent clones could be distinguished by a differential expression of CD90. Altogether, isolation of these clonal lines allowed demonstrating the coexistence of multipotential and restricted-lineage progenitors in the mouse pulp. These cells may further permit unravelling specificities of the different types of pulp progenitors, hence facilitating the development of cell-based therapies of the dental pulp or other cranio-facial tissues.
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Diferenciación Celular , Pulpa Dental , Células Madre Multipotentes , Osteogénesis , Animales , Linaje de la Célula , Pulpa Dental/citología , Pulpa Dental/crecimiento & desarrollo , Humanos , Ratones , Ratones Transgénicos , Diente Molar/citología , Diente Molar/crecimiento & desarrollo , Células Madre Multipotentes/citología , Células Madre Multipotentes/metabolismo , Odontoblastos/citología , Odontoblastos/metabolismo , Osteogénesis/fisiologíaRESUMEN
Binary interactions dominate the evolution of massive stars, but their role is less clear for low- and intermediate-mass stars. The evolution of a spherical wind from an asymptotic giant branch (AGB) star into a nonspherical planetary nebula (PN) could be due to binary interactions. We observed a sample of AGB stars with the Atacama Large Millimeter/submillimeter Array (ALMA) and found that their winds exhibit distinct nonspherical geometries with morphological similarities to planetary nebulae (PNe). We infer that the same physics shapes both AGB winds and PNe; additionally, the morphology and AGB mass-loss rate are correlated. These characteristics can be explained by binary interaction. We propose an evolutionary scenario for AGB morphologies that is consistent with observed phenomena in AGB stars and PNe.
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Insulin receptor (IR)-deficient pups rapidly become hyperglycemic and hyperinsulinemic and die of diabetic ketoacidosis within a few days. Immunocytochemical analysis of the endocrine pancreas revealed that IR deficiency did not alter islet morphology or the number of beta-, alpha-, delta-, and pancreatic polypeptide (PP) cells. The lack of IR did not result in major changes in the expression of islet hormone genes or of beta-cell-specific marker genes encoding pancreas duodenum homeobox-containing transcription factor-1 (PDX-1), glucokinase (GCK), and GLUT2, as shown by reverse transcriptase-polymerase chain reaction analysis. The serum glucagon levels in IR-deficient and nondiabetic littermates were comparable. Finally, total insulin content in the pancreas of IR-deficient pups was gradually depleted, indicating sustained insulin secretion, not compensated for by increased insulin biosynthesis. These findings are discussed in light of recent results suggesting a role of IR in beta-cell function.
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Proteínas de Homeodominio , Islotes Pancreáticos/metabolismo , Receptor de Insulina/genética , Animales , Animales Recién Nacidos , Femenino , Expresión Génica , Genotipo , Glucagón/genética , Glucagón/metabolismo , Glucoquinasa/genética , Transportador de Glucosa de Tipo 2 , Hiperinsulinismo/genética , Hiperinsulinismo/metabolismo , Inmunohistoquímica , Insulina/genética , Insulina/metabolismo , Islotes Pancreáticos/química , Masculino , Ratones , Ratones Noqueados , Ratones Mutantes , Proteínas de Transporte de Monosacáridos/genética , Polipéptido Pancreático/genética , Polipéptido Pancreático/metabolismo , Fenotipo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptor de Insulina/deficiencia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Somatostatina/genética , Somatostatina/metabolismo , Transactivadores/genéticaRESUMEN
We have derived skeletal muscle cell lines from wild-type (wt) and insulin receptor (IR) knockout mice to unravel the metabolic potential of IGF-1 receptor (IGF-1R). Both wt and IR(-/-) myoblasts differentiated into myotubes with similar patterns of expression of muscle-specific genes such as MyoD, myogenin and MLC1A indicating that IR is not required for this process. Binding of 125I-IGF-1 on wt and IR(-/-) myotubes was similar showing that IGF-1R was not upregulated in the absence of IR. Stimulation of IR(-/-) myotubes with IGF-1 (10(-10) to 10(-7) M) increased glucose uptake and incorporation into glycogen, induced IRS-1 phosphorylation and activated PI 3-kinase and MAP kinase, two enzymes of major signaling pathways. These effects were comparable to those obtained with wt myotubes using insulin or IGF-1 or with IR(-/-) myotubes using insulin at higher concentrations. This study provides a direct evidence that IGF-1R can represent an alternative receptor for metabolic signaling in muscle cells.
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Eliminación de Gen , Músculo Esquelético/metabolismo , Receptor IGF Tipo 1/metabolismo , Receptor de Insulina/deficiencia , Animales , Animales Recién Nacidos , Sitios de Unión , Biomarcadores , Células Cultivadas , Medio de Cultivo Libre de Suero , Desoxiglucosa/metabolismo , Glucosa/metabolismo , Glucógeno/metabolismo , Insulina/farmacología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/farmacología , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Músculo Esquelético/citología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/enzimología , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación/efectos de los fármacos , ARN Mensajero/análisis , ARN Mensajero/genética , Receptor de Insulina/genética , Transducción de Señal/efectos de los fármacosRESUMEN
Cell systems derived from knockout mice for the insulin receptor (IR) or the IGF-1 receptor (IGF-1R) represent unique tools for dissecting complex interplay in the actions of insulin and insulin-like growth factors through their cognate versus non-cognate receptor. In this study, we used a fibroblast cell line derived from IR-deficient mice to investigate metabolic and mitogenic effects of IGF-1 and insulin. IGF-1 was able to stimulate glucose uptake, glucose incorporation into glycogen and thymidine incorporation in such cells. Phosphatidylinositol 3-kinase and mitogen-activated protein kinase, two enzymes of major metabolic-mitogenic signaling pathways, were activated upon stimulating these cells with IGF-1. All these effects were also achieved when IR-deficient cells were stimulated with insulin. Thus, IGF-1R can represent an alternative receptor through which insulin might exert some of its effects.
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Factor I del Crecimiento Similar a la Insulina/farmacología , Insulina/farmacología , Receptor de Insulina/deficiencia , Animales , Línea Celular , Fibroblastos/citología , Fibroblastos/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Ratones , Ratones Noqueados , Mitógenos/farmacología , Receptor IGF Tipo 1/efectos de los fármacos , Receptor IGF Tipo 1/metabolismo , Receptor de Insulina/metabolismo , Transducción de Señal/efectos de los fármacos , Timidina/metabolismoRESUMEN
Since the summer of 2000, vertical oozing cankers have been observed on trunks and branches of Persian walnut trees (Juglans regia). Cvs. Fernor, Chandler, Mayette, and Hartley were the most frequently affected, but cvs. Lara and Franquette could also be affected. Brenneria nigrifluens (synonym Erwinia nigrifluens) (3) was isolated from diseased trees from 13 orchards and nurseries in southwestern (Aquitaine, Périgord, Charentes, and Quercy), southeastern (Grenoble areas), and western (near Angers) France. Cankers were observed on trunks and branches where brown-to-black exudates staining the bark appeared mainly in the summer. Isolations were performed primarily from exudates but also from infected tissues by using King's medium B. Colonies similar in appearance to Brenneria nigrifluens (1) were purified and characterized. Gram reaction, Kovac's oxidase, oxidative-fermentative metabolism, and urease activity were assayed for all isolates. API Biotype 100 kits (BioMérieux, Marcy l'Etoile, France) were used as recommended, except that incubations were at 28°C for 4 days. When compared with the reference strain (French Collection of Plant Pathogenic Bacteria (CFBP) 4998T = National Collection of Plant Pathogenic Bacteria (NCPPB) 564T = American Type Culture Collection (ATCC) 13028T) from California, 14 isolated strains were identified as B. nigrifluens on the basis of physiological and biochemical characteristics. These 14 strains were deposited in the CFBP under Accession Nos. 6746 to 6759. Pathogenicity of three selected strains (CFBP 6746, 6747, and 6758) was confirmed by inoculating branches of 7-year-old walnut trees with 108 CFU of each isolate introduced in wounds (2). The reference strain (CFBP 4998T) and water were similarly inoculated as controls. Two and five months later, necrotic lesions were observed in the inner bark and dark lines were observed in internal wood, but no external cankers were observed on any trees inoculated with the local and reference strains. B. nigrifluens was reisolated from the dark lines in internal wood up to approximately 10 cm from the inoculation site. To our knowledge, this is the first report of this bacterium in France. References: (1) L. Hauben et al. Syst. Appl. Microbiol. 21:384, 1998. (2) M. Ridé and S. Ridé. Proc. Int. Conf. Plant Pathogenic Bacteria, 4th, 2:957, 1978. (3) E. E. Wilson et al. Phytopathology 47:669, 1957.
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On chest radiographs, the precise assessment of thoracic injuries consecutive to blunt trauma is often compromised by the nonspecific appearance of many lesions. Furthermore, significant injuries are frequently overlooked. However, the management of the patients with chest trauma is still often based primarily upon clinical and radiographic findings and Computed Tomography (CT) is often performed secondarily on the basis of unexplained clinical signs or suspected radiographic abnormality. Some authors have reported that CT was a highly sensitive method for detecting thoracic lesions frequently not seen or underestimated on conventional supine chest radiographs. However, the value that these new CT findings could have in the therapeutic management of these patients, have not been systematically investigated to our knowledge, except in a limited series suggesting that the course of critically ill patients could be substantially altered after thoracic CT. In order to estimate the role of early CT in the management of patient care, we report the therapeutic consequences of CT findings in forty patients who we report the therapeutic consequences of CT findings in forty patients who had a thoracic CT within few hours following a chest injury. We showed that early thoracic CT scan in patients with blunt trauma detected significantly more lesions than did chest X-Ray and appreciably modified the treatment modalities in 70% of our patients. We then recommend that all the patients admitted in ICU after chest trauma undergo a thoracic CT scan as soon as possible in order to optimize their treatment modalities.
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Traumatismos Torácicos/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adolescente , Adulto , Anciano , Contusiones/diagnóstico por imagen , Urgencias Médicas , Estudios de Evaluación como Asunto , Femenino , Fracturas Óseas/diagnóstico por imagen , Hemotórax/diagnóstico por imagen , Humanos , Lesión Pulmonar , Masculino , Persona de Mediana Edad , Neumotórax/diagnóstico por imagen , Rotura , Traumatismos Torácicos/terapiaRESUMEN
In the field of dentistry, the murine incisor has long been considered as an outstanding model to study amelogenesis. However, it clearly appears that enamel from wild type mouse incisors and molars presents several structural differences. In incisor, exclusively radial enamel is observed. In molars, enamel displays a high level of complexity since the inner part is lamellar whereas the outer enamel shows radial and tangential structures. Recently, the serotonin 2B receptor (5-HT2BR) was shown to be involved in ameloblast function and enamel mineralization. The incisors from 5HT2BR knockout (KO) mice exhibit mineralization defects mostly in the outer maturation zone and porous matrix network in the inner zone. In the molars, the mutation affects both secretory and maturation stages of amelogenesis since pronounced alterations concern overall enamel structures. Molars from 5HT2BR KO mice display reduction in enamel thickness, alterations of inner enamel architecture including defects in Hunter-Schreger Bands arrangements, and altered maturation of the outer radial enamel. Differences of enamel structure were also observed between incisor and molar from other KO mice depleted for genes encoding enamel extracellular matrix proteins. Thus, upon mutation, enamel analysis based exclusively on incisor defects would be biased. In view of the functional relationship between enamel structure and tooth morphogenesis, identification of molecular actors involved in amelogenesis requires comparative studies between mice molars and incisors.
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Serotonin reuptake inhibitor (SRI) antidepressants such as fluoxetine (Prozac), promote hippocampal neurogenesis. They also increase the levels of the bcl-2 protein, whose overexpression in transgenic mice enhances adult hippocampal neurogenesis. However, the mechanisms underlying SRI-mediated neurogenesis are unclear. Recently, we identified the microRNA miR-16 as an important effector of SRI antidepressant action in serotonergic raphe and noradrenergic locus coeruleus (LC). We show here that miR-16 mediates adult neurogenesis in the mouse hippocampus. Fluoxetine, acting on serotonergic raphe neurons, decreases the amount of miR-16 in the hippocampus, which in turn increases the levels of the serotonin transporter (SERT), the target of SRI, and that of bcl-2 and the number of cells positive for Doublecortin, a marker of neuronal maturation. Neutralization of miR-16 in the hippocampus further exerts an antidepressant-like effect in behavioral tests. The fluoxetine-induced hippocampal response is relayed, in part, by the neurotrophic factor S100ß, secreted by raphe and acting via the LC. Fluoxetine-exposed serotonergic neurons also secrete brain-derived neurotrophic factor, Wnt2 and 15-Deoxy-delta12,14-prostaglandin J2. These molecules are unable to mimic on their own the action of fluoxetine and we show that they act synergistically to regulate miR-16 at the hippocampus. Of note, these signaling molecules are increased in the cerebrospinal fluid of depressed patients upon fluoxetine treatment. Thus, our results demonstrate that miR-16 mediates the action of fluoxetine by acting as a micromanager of hippocampal neurogenesis. They further clarify the signals and the pathways involved in the hippocampal response to fluoxetine, which may help refine therapeutic strategies to alleviate depressive disorders.
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Conducta Animal/fisiología , Trastorno Depresivo Mayor/genética , Fluoxetina/farmacología , Hipocampo/efectos de los fármacos , MicroARNs/fisiología , Núcleos del Rafe/fisiología , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Transducción de Señal/genética , Adulto , Animales , Conducta Animal/efectos de los fármacos , Trastorno Depresivo Mayor/tratamiento farmacológico , Femenino , Fluoxetina/administración & dosificación , Hipocampo/metabolismo , Humanos , Locus Coeruleus/efectos de los fármacos , Locus Coeruleus/metabolismo , Masculino , Ratones , Núcleos del Rafe/efectos de los fármacos , Núcleos del Rafe/cirugíaAsunto(s)
Insulina/genética , Receptor de Insulina/genética , Animales , Animales Recién Nacidos , Homocigoto , Ratones , MutaciónRESUMEN
The genetic manipulation of mice has become an essential and elegant method for studying the function of proteins in physiology, and for testing the veracity of information obtained from cell culture experiments. During the past few years, a variety of transgenic and knockout mouse models of PKB (protein kinase B)/Akt have been generated and investigated. In this paper, we focus on the phenotypes of these PKB/Akt overexpression and mutant mice that may help to elucidate the functions exerted by PKB/Akt in mammals.
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Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/fisiología , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/fisiología , Animales , Encéfalo/patología , Diabetes Mellitus/patología , Modelos Animales de Enfermedad , Femenino , Humanos , Linfoma/patología , Masculino , Glándulas Mamarias Animales/metabolismo , Ratones , Ratones Noqueados , Ratones Transgénicos , Leche/metabolismo , Mutación , Miocardio/metabolismo , Fenotipo , Neoplasias de la Próstata/metabolismo , Proteínas Proto-Oncogénicas c-akt , Neoplasias del Timo/patologíaRESUMEN
AIMS/HYPOTHESIS: Insulin receptor null mutant mice develop severe diabetes, ketoacidosis and liver steatosis and die within 1 week after birth. Since the liver plays an essential role in the control of glucose homeostasis, we examined in this work whether the metabolic disorders of insulin receptor-deficient mice could be improved upon restoration of hepatic glucose metabolism by transgenic constitutive overexpression of glucokinase selectively in the liver. METHODS: We first generated transgenic mice overexpressing rat glucokinase cDNA under control of the liver-specific phenylalanine hydroxylase gene promoter. These transgenic mice were crossed with heterozygous insulin-receptor-null mutants to produce homozygous insulin-receptor-null mice overexpressing glucokinase in the liver. RESULTS: The transgenic mice overexpressing glucokinase in the liver showed improved glucose tolerance and were mildly hypoglycaemic and hyperlipidaemic under starved conditions. The introduction of the glucokinase transgene in insulin receptor null mice did not prevent the development of glycosuria. However, ketoacidosis was delayed by more than 1 week and survival was prolonged to 10 to 16 days in 16% of the pups. In these longer surviving pups, serum glucose and triglyceride concentrations were lowered, hepatic glycogen stores were reconstituted and liver steatosis was absent as compared with the pups which had developed strong ketoacidosis and died earlier. CONCLUSIONS/INTERPRETATION: These results show that overexpression of hepatic glucokinase can compensate, in part, for the metabolic disorders developed by insulin receptor-deficient mice. This shows the importance of improving hepatic function in diabetes and must revive interest in enhancement of glucokinase activity as a therapeutic strategy for the treatment of diabetes.
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Glucemia/metabolismo , Glucoquinasa/genética , Receptor de Insulina/deficiencia , Receptor de Insulina/fisiología , Animales , Secuencia de Bases , Clonación Molecular , Cruzamientos Genéticos , ADN Complementario , Cetoacidosis Diabética/genética , Glucoquinasa/metabolismo , Prueba de Tolerancia a la Glucosa , Glucosuria/genética , Homocigoto , Humanos , Hígado/citología , Hígado/enzimología , Ratones , Ratones Noqueados , Ratones Transgénicos , Especificidad de Órganos , Fenilalanina Hidroxilasa/genética , Regiones Promotoras Genéticas , Ratas , Receptor de Insulina/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
The expression of a number of genes encoding key players in insulin signalling and action, including insulin, insulin receptor (IR), downstream signalling molecules such as insulin receptor substrate-1 (IRS-1) and IRS-2, glucose transporters (GLUT4, GLUT2) and important metabolic enzymes such as glucokinase, has now been altered in transgenic or knockout mice. Such mice presented with phenotypes ranging from mild defects, revealing complementarity between key molecules or pathways, to severe diabetes with ketoacidosis and early postnatal death. Insulin action could also be improved by overproduction of proteins acting at regulatory steps. The development of diabetes by combining mutations, which alone do not lead to major metabolic alterations, validated the 'diabetogenes' concept of non-insulin-dependent diabetes mellitus. Genes encoding insulin-like growth factors (IGF-I and IGF-II) and their type I receptor (IGF-IR) have also been disrupted. It appears that although IR and IGF-IR are both capable of metabolic and mitogenic signalling, they are not fully redundant. However, IR could replace IGF-IR if efficiently activated by IGF-II. Studies with cell lines lacking IR or IGF-IR lend support to such conclusions. Concerning the issues of specificity and redundancy, studies with cell lines derived from IRS-1-deficient mice showed that IRS-1 and IRS-2 are also not completely interchangeable.
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Insulina/metabolismo , Ratones Noqueados/genética , Ratones Transgénicos/genética , Proteínas Musculares , Receptor de Insulina/genética , Transducción de Señal , Animales , Ingeniería Genética , Transportador de Glucosa de Tipo 2 , Transportador de Glucosa de Tipo 4 , Insulina/genética , Proteínas Sustrato del Receptor de Insulina , Péptidos y Proteínas de Señalización Intracelular , Ratones , Ratones Mutantes , Proteínas de Transporte de Monosacáridos/genética , Proteínas de Transporte de Monosacáridos/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Receptor de Insulina/metabolismo , Somatomedinas/genética , Somatomedinas/metabolismoRESUMEN
Transgenic and gene targeting approaches have now been applied to a number of genes in order to investigate the metabolic disorders that would result by manipulating insulin action or pancreatic beta-cell function in the mouse. The availability of such mutant mice will allow in the future to develop animal models in which the pathophysiologies resulting from polygenic defects might be reconstituted and studied in detail. Such animal models hopefully will lead to better understanding of complex polygenic diseases such as non-insulin-dependent diabetes mellitus (NIDDM).