RESUMEN
Insulin secretion from MIN6 cells configured as cell aggregates by culture on a gelatin substrate (pseudoislets) is enhanced compared to that of MIN6 cells grown as monolayers on tissue culture plastic, indicating the importance of beta-cell-to-beta-cell proximity for insulin release. In this study we have shown that glucose induced a biphasic release of insulin from pseudoislets, whereas the amplitude and duration of the responses of equivalent monolayer cells were much reduced. Purinergic aqonists have been implicated in intercellular communication between beta-cells, so we investigated whether adenine nucleotides co-released with insulin are responsible for the enhanced secretory responses of pseudoislets. We have demonstrated that MIN6 cells express purinergic A(1) and P2Y receptors, and that adenine nucleotides increased [Ca(2+)](i) with an efficacy of agonists being ATP > ADP > AMP. However, neither suramin nor the more selective A(1) antagonist 1,3-dipropyl-8-cyclopentylxanthine reduced glucose-induced insulin secretion from pseudoislets, and stimulation of monolayer cells with a range of adenine nucleotides did not enhance glucose-induced secretion. These results suggest that enhanced secretion from MIN6 pseudoislets is not due to increased paracrine/autocrine action of adenine nucleotides.
Asunto(s)
Nucleótidos de Adenina/fisiología , Insulina/metabolismo , Islotes Pancreáticos/metabolismo , Nucleótidos de Adenina/metabolismo , Nucleótidos de Adenina/farmacología , Animales , Comunicación Autocrina , Calcio/metabolismo , Línea Celular , Glucoquinasa/análisis , Glucosa/farmacología , Transportador de Glucosa de Tipo 2 , Secreción de Insulina , Islotes Pancreáticos/citología , Islotes Pancreáticos/efectos de los fármacos , Cinética , Ratones , Proteínas de Transporte de Monosacáridos/análisis , Comunicación ParacrinaRESUMEN
UNLABELLED: Isolated atrial flutter is an extremely rare form of supraventricular tachycardia in the neonatal period. It may be initiated by central venous catheterization. CASE REPORT: A male infant was born at 35 weeks by cesarean section for placenta praevia. He was eutrophic. Apgar score was 10 at 1 and 5 minutes. He secondary developed a respiratory distress syndrome. He was then ventilated by nasal CPAP. Immediately after an umbilical venous catheterization, a tachycardia appeared without preexistent cardiac dysfunction. An intravenous dose of adenosine (Striadyne) showed a characteristic sawtooth pattern of P waves on inferior leads. The cardiac-US examination was normal. This atrial flutter was converted to normal sinus rhythm by transoesophageal pacing, without adjunction of antiarrhythmic drugs. The newborn was weaned from mechanical ventilation 48 hours later and discharged from hospital at seven days post natal age. His development and clinical examination were normal two months later. CONCLUSION: The isolated atrial flutter is rare in the neonate. It may be triggered by a venous catheterization. Transoesophageal atrial pacing is safe and effective for conversion.
Asunto(s)
Aleteo Atrial/etiología , Cateterismo/efectos adversos , Venas Umbilicales , Adenosina , Factores de Edad , Antiarrítmicos , Puntaje de Apgar , Aleteo Atrial/diagnóstico , Aleteo Atrial/terapia , Estimulación Cardíaca Artificial , Cesárea , Electrocardiografía , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Factores de TiempoRESUMEN
Nitric oxide synthase, induced by cytokines in insulin-containing cells, produces nitric oxide which inhibits function and may promote cell killing. Since glucagon was shown to prevent inducible nitric oxide synthase (iNOS) expression in rat hepatocytes it was of interest to examine the action of glucagon (and cyclic AMP) on iNOS induction in insulin-producing cells. Cultured RIN5F cells and primary rat and human islets of Langerhans were treated with interleukin 1beta (IL-1beta) or a combination of cytokines, and were co-treated or pre-treated with glucagon. In RIN5F cells, the activity of iNOS induced by IL-1beta (10 pM, 24 h), was significantly reduced by glucagon (1000 nM), which raises cyclic AMP, and by forskolin (1-10 microM), a non specific activator of adenylate cyclase. Glucagon and forskolin also decreased iNOS expression in RIN5F cells, and rat and human islets, as shown by Western blotting. The inhibitory action of IL-1beta (100 pM, 24 h) on rat islet insulin secretion was partially reversed by 1-h pre-treatment with glucagon (10-1000 nM), while the contrasting stimulatory effect of 48-h treatment with cytokines on insulin secretion from human islets was similarly prevented by glucagon (1000 nM) pre-treatment. These results suggest that glucagon inhibits iNOS expression in insulin-containing cells and imply that glucagon could modulate the inhibitory effects of cytokines.
Asunto(s)
Citocinas/farmacología , Regulación Enzimológica de la Expresión Génica/fisiología , Glucagón/farmacología , Insulina/metabolismo , Interleucina-1/farmacología , Islotes Pancreáticos/fisiología , Óxido Nítrico Sintasa/biosíntesis , Animales , Células Cultivadas , Colforsina/farmacología , AMP Cíclico/metabolismo , Inducción Enzimática , Femenino , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Humanos , Secreción de Insulina , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Cinética , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa de Tipo II , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Células Tumorales CultivadasRESUMEN
Dyschondrosteosis is an autosomal dominant form of mesomelic dysplasia that is often combined with a deformity of the forearms called Madelung deformity. Based on the observation of X-Y translocations (p22,q12) in patients with dyschondrosteosis, the authors tested the pseudoautosomal region in eight affected families and showed linkage of the dyschondrosteosis gene to a microsatellite DNA marker at the DXYS233 locus (Zmax = 6.26 at theta = 0). Since the short stature homeobox-containing gene (SHOX) involved in idiopathic growth retardation and possibly Turner syndrome maps to this region, SHOX was regarded as a strong candidate gene for dyschondrosteosis. This article reports the detection of large-scale SHOX deletions in seven of the eight families and a nonsense mutation of SHOX in the remaining family affected with dyschondrosteosis. Additional evidence suggests that Langer mesomelic dwarfism results from homozygous mutations at the genetic locus responsible for dyschondrosteosis.
Asunto(s)
Enfermedades Óseas/genética , Deleción Cromosómica , Antebrazo/anomalías , Trastornos del Crecimiento/genética , Proteínas de Homeodominio/genética , Niño , Enanismo/genética , Ligamiento Genético , Humanos , Repeticiones de Microsatélite , Mutación , Linaje , Proteína de la Caja Homeótica de Baja Estatura , SíndromeRESUMEN
Dyschondrosteosis (DCS) is an autosomal dominant form of mesomelic dysplasia with deformity of the forearm (Madelung deformity; ref. 3). Based on the observation of XY translocations (p22,q12; refs 4-6) in DCS patients, we tested the pseudoautosomal region in eight families with DCS and showed linkage of the DCS gene to a microsatellite DNA marker at the DXYS233 locus (Zmax=6.26 at theta=0). The short stature homeobox-containing gene (SHOX), involved in idiopathic growth retardation and possibly Turner short stature, maps to this region and was therefore regarded as a strong candidate gene in DCS. Here, we report large-scale deletions (in seven families) and a nonsense mutation (in one family) of SHOX in patients with DCS and show that Langer mesomelic dwarfism results from homozygous mutations at the DCS locus.
Asunto(s)
Proteínas de Homeodominio/genética , Mutación , Osteocondrodisplasias/genética , Femenino , Genotipo , Humanos , Hibridación Fluorescente in Situ , Masculino , Datos de Secuencia Molecular , Linaje , Proteína de la Caja Homeótica de Baja Estatura , Translocación Genética , Cromosoma X , Cromosoma YRESUMEN
We have previously observed that treatment of rat islets of Langerhans with interleukin-1beta for 12 h results in nitric oxide-dependent inhibition of insulin secretion, while 48 h treatment increased rates of islet cell death by apoptosis. Here, we demonstrate that interleukin-1beta-mediated nitric oxide formation and inhibition of insulin secretion are significantly reduced by 24 h pretreatment of rat islets of Langerhans with insulin-like growth factor I (IGF-I). IGF-I decreased cytokine induction of nitric oxide synthase in islets. Use of an arginine analogue in culture or IGF-I pretreatment of islets were also effective in protecting islets against cytokine-mediated apoptotic cell death. We conclude that IGF-I antagonises inhibitory and cytotoxic effects of cytokines in rat islets.