RESUMEN

BACKGROUND: The aim of this study was to investigate the association of oxytocin with trait and state psychological factors in type 2 diabetic patients. METHODS: OXT and psychological variables were analyzed from 86 controlled diabetic patients (glycosylated haemoglobin A1c (HbA1c) < 7%) from 45 uncontrolled diabetic patients (HbA1c ≥ 7). Psychological characteristics were assessed with the Eysenck Personality Questionnaire (EPQ), while state psychological characteristics were measured with the Symptom Checklist 90-R (SCL 90-R). Blood samples were taken for measuring oxytocin in both subgroups during the initial phase of the study. One year later, the uncontrolled diabetic patients were reevaluated with the use of the same psychometric instruments. RESULTS: During the first evaluation of the uncontrolled diabetic patients, a statistically significant positive relationship between the levels of OXT and psychoticism in EPQ rating scale (P < 0.013) was observed. For controlled diabetic patients, a statistically significant negative relationship between oxytocin and somatization (P < 0.030), as well as obsessive-compulsive scores (P < 0.047) in SCL-90 rating scale, was observed. During the second assessment, the values of OXT decreased when the patients managed to control their metabolic profile. CONCLUSIONS: The OXT is in association with psychoticism, somatization, and obsessionality may be implicated in T2DM.

Asunto(s)

Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Hiperglucemia/prevención & control , Trastorno Obsesivo Compulsivo/complicaciones , Oxitocina/sangre , Trastornos Psicóticos/complicaciones , Trastornos Somatomorfos/complicaciones , Anciano , Estudios Transversales , Diabetes Mellitus Tipo 2/psicología , Diabetes Mellitus Tipo 2/terapia , Regulación hacia Abajo , Femenino , Hemoglobina Glucada/análisis , Grecia , Hospitales Universitarios , Humanos , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/etiología , Servicio Ambulatorio en Hospital , Escalas de Valoración Psiquiátrica , Trastornos Psicóticos/etiología , Trastornos Somatomorfos/etiología

RESUMEN

Adiponectin, an adipose tissue secreted protein, exhibits anti-inflammatory and antiatherogenic properties. We examined the effects of the globular and full-length adiponectin on cytokine production in macrophages derived from Coronary Artery Disease (CAD) patients and control individuals. Adiponectin's effects in human macrophages upon lipopolysaccharide (LPS) treatment were also examined. Full length adiponectin acted differently on TNF-α and IL-6 production by upregulating TNF-α and IL-6 protein production, but not their mRNA expression. Additionally, full length adiponectin was unable to abrogate LPS proinflammatory effect in TNF-α and IL-6 mRNA expression in CAD and NON-CAD macrophages. In contrast, globular adiponectin appeared to have proinflammatory properties by potently upregulating TNF-α and IL-6 mRNA and protein secretion in human macrophages while subsequently rendered cells resistant to further proinflammatory stimuli. Moreover, both forms of adiponectin powerfully suppressed scavenger MSR-AI mRNA expression and augmented IL-10 protein release, both occurring independently of the presence of LPS or CAD. These data indicate that adiponectin could potentially protect human macrophages via the elevated IL-10 secretion and the suppression of MSR-AI expression. It can also be protective in CAD patients since the reduced adiponectin-induced IL-6 release in CAD macrophages compared to controls, could be beneficial in the development of inflammation related atherosclerosis.

Asunto(s)

Adiponectina/farmacología , Enfermedad de la Arteria Coronaria/patología , Interleucina-10/biosíntesis , Interleucina-6/biosíntesis , Macrófagos/metabolismo , Factor de Necrosis Tumoral alfa/biosíntesis , Animales , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Ratones , Persona de Mediana Edad , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Depuradores de Clase A/genética , Receptores Depuradores de Clase A/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

Visfatin, is a new adipokine, highly expressed in the visceral fat of both mice and humans. To examine whether visfatin is expressed in human peripheral monocyte-enriched mononuclear cells and whether its expression is altered in type 2 diabetes (DM2), we compared 24 DM2 women [17 overweight (BMI >25) and 7 lean (BMI<25)] to 26 healthy women (14 overweight and 12 lean), all premenopausal. Relative visfatin mRNA levels were significantly higher (approximately 3-fold) in DM2 compared to healthy control women (p<0.02), independently of the presence of overweight/obesity. Mononuclear TNF-alpha and IL-6 mRNA expression was also elevated in DM2 compared to control women (p=0.001 and p=0.004, respectively), an increase observed in both lean and overweight DM2 women. By contrast, circulating visfatin, TNF-alpha, and IL-6 levels showed no difference between DM2 and control women, while adiponectin plasma levels were significantly decreased in the DM2 women (p<0.001). Circulating visfatin and TNF-alpha levels did not differ either between the lean and the overweight subgroups of DM2 and control women, while IL-6 plasma levels were significantly higher in both overweight subgroups compared to their lean counterparts. In conclusion, visfatin, TNF-alpha, and IL-6 mRNA expressions are increased in peripheral mononuclear-monocytic cells from women with type 2 diabetes, independent of their BMI, which may enhance the effects of their adipose-derived levels and may contribute to the increased insulin resistance and atherogenic risk of these patients.

Asunto(s)

Diabetes Mellitus Tipo 2/genética , Interleucina-6/genética , Leucocitos Mononucleares/metabolismo , Nicotinamida Fosforribosiltransferasa/genética , Factor de Necrosis Tumoral alfa/genética , Adulto , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Regulación de la Expresión Génica , Humanos , Interleucina-6/sangre , Interleucina-6/metabolismo , Leucocitos Mononucleares/patología , Persona de Mediana Edad , Nicotinamida Fosforribosiltransferasa/sangre , Nicotinamida Fosforribosiltransferasa/metabolismo , Sobrepeso/sangre , Sobrepeso/complicaciones , Sobrepeso/genética , Sobrepeso/metabolismo , ARN Mensajero/metabolismo , Delgadez/sangre , Delgadez/genética , Delgadez/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

BACKGROUND: Tumor necrosis factor alpha (TNFalpha), a cytokine produced at inflammatory sites and in adipose tissue, is known primarily for its detrimental effects on insulin action. There is evidence to suggest that TNFalpha may also influence beta-cell function. Leptin is another adipose tissue-derived hormone that might also act on beta-cells. OBJECTIVE: We explored the independent and combined effects of TNFalpha and leptin upon basal and glucose-stimulated insulin transcription and secretion in the HIT-T15 pancreatic beta cell line. METHODS: Cells were cultured for 40 h in the presence of near-normal basal (7 mM) or high (16.7 mM) glucose and treated with either TNFalpha (1, 10 and 50 ng/ml) or leptin (10, 50 and 100 ng/ml) or both together. Insulin concentrations were measured by radioimmunoassay. Insulin mRNA levels were evaluated by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method, after normalization with beta-actin mRNA. RESULTS: TNFalpha significantly suppressed basal and glucose-stimulated insulin secretion and proinsulin mRNA transcription in a dose-dependent manner, an effect that was more powerful in the presence of high glucose. Leptin also inhibited dose-dependent insulin mRNA and protein at both glucose concentrations, but did not appear to further potentiate the suppressive effects of TNFalpha. CONCLUSION: TNFalpha suppresses both basal and glucose-stimulated insulin transcription and secretion in HIT-T15 cells, an effect that is enhanced significantly by high glucose. Leptin also independently inhibits basal and glucose-stimulated insulin secretion and transcription but does not modify TNFalpha effects. These effects might contribute to the abnormalities of glucose metabolism that characterize conditions of increased TNFalpha and/or leptin production.

Asunto(s)

Insulina/genética , Insulina/metabolismo , Leptina/farmacología , ARN Mensajero/análisis , Factor de Necrosis Tumoral alfa/farmacología , Línea Celular , Relación Dosis-Respuesta a Droga , Glucosa , Secreción de Insulina , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Radioinmunoensayo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transcripción Genética

RESUMEN

Leptin, the adipocyte-derived hormone, is secreted into the blood and regulates body weight via its receptors in the hypothalamus. Leptin receptors are also present in many peripheral tissues implicating leptin in the regulation of other body functions, including reproduction, liver and enteric metabolism, hematopoiesis, and immunity. Four splice variants of the leptin receptor have been identified in humans: the long isoform that has full intracellular signaling capacity and 3 shorter isoforms that differ in the length of their cytoplasmic tail. Here, we report the quantification by reverse transcriptase-polymerase chain reaction (RT-PCR) of the relative expression levels of the 2 major leptin receptor splice variants, the long (OB-RL) and the shortest membrane bound variant (OB-RS) in mononuclear cells from peripheral blood of 15 healthy human subjects (9 women and 6 men), with a body mass index (BMI) that ranged from 19.7 to 41.6. Both OB-RL and OB-RS were coexpressed in all mRNAs tested. However, the expression of the short form (OB-RS), was on average 8-fold higher than the expression of the long form (OB-RL) (120.8 +/- 12.9 v 14.6 +/- 3.0 relative intensity units, P < .001). The predominance of the short splice variant over the long one was apparent in all samples and ranged from 4- to 27-fold. There was no significant difference in the expression of either isoform between men and women. However, the relative expression of both OB-RS and OB-RL isoforms was significantly lower in the overweight (BMI > 26), compared with the lean subjects (BMI < 25) (78.8 +/- 9.1 and 6.2 +/- 1.1 v148.8 +/- 14.4 and 18.9 +/- 4.0 relative intensity units, respectively, P < .03) and was inversely correlated with the BMI and plasma leptin levels (P < .01). In conclusion, the expression of OB-RS and OB-RL leptin receptor isoforms appears to be reduced in human peripheral blood mononuclear cells from obese individuals, with OB-RS remaining the predominant leptin receptor isoform. This might have implications for the bioavailability and/or action of circulating leptin not only on these cells, but also on other target tissues.

Asunto(s)

Proteínas Portadoras/sangre , Monocitos/metabolismo , Receptores de Superficie Celular , Adulto , Índice de Masa Corporal , Proteínas Portadoras/genética , Proteínas Portadoras/fisiología , ADN Recombinante , Femenino , Variación Genética , Humanos , Leptina/sangre , Masculino , Isoformas de Proteínas/sangre , ARN Mensajero/sangre , Receptores de Leptina , Valores de Referencia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Delgadez

RESUMEN

Cell adhesion molecules belonging to the immunoglobulin superfamily promote cell aggregation and neurite outgrowth. These proteins are multidomain molecules comprising a number of distinct modules, notably Ig domains of the C2 class and fibronectin type III repeats. A subgroup of these neural adhesion molecules are linked to the membrane with a glycosylphosphatidylinositol anchor and show a more restricted pattern of expression in the embryo. Among them, the human homologue of the transient axonal glycoprotein, named TAX-1, shares a great degree of similarity at the protein level with rodent TAG-1. In the present study we set out to determine which domains of TAX-1 are involved in promoting the homophilic, adhesive properties of the molecule. We established stable Schneider-2 cell lines expressing the intact molecule, the fibronectin, or the immunoglobulin domains. The fibronectin domains were necessary and sufficient to mediate homophilic binding and induce cell aggregation, a response also observed with cells expressing the intact TAX-1 molecule. Aggregation was inhibited by the secreted form of the TAG-1 protein. On the other hand, the immunoglobulin domains by themselves were not able to induce cell aggregation. In addition, TAX-1 was localized in areas of cell contact among aggregating cells, justifying its role as an adhesion molecule.

Asunto(s)

Moléculas de Adhesión Celular Neuronal/metabolismo , Fibronectinas/metabolismo , Sustancias de Crecimiento/metabolismo , Glicoproteínas de Membrana/metabolismo , Moléculas de Adhesión Celular Neuronal/genética , Línea Celular , Contactina 2 , ADN Complementario , Sustancias de Crecimiento/genética , Humanos , Inmunoglobulinas/metabolismo , Glicoproteínas de Membrana/genética , Fosfatidilinositol Diacilglicerol-Liasa , Hidrolasas Diéster Fosfóricas/metabolismo , Unión Proteica

RESUMEN

The transient axonal glycoprotein (TAG-1) is a cell adhesion molecule that promotes neurite outgrowth and belongs to the immunoglobulin superfamily. We have isolated cDNAs encoding TAX1, the human homologue of TAG-1. Human TAX1 shows a high degree of homology to rat TAX1 and less to its chick counterpart, axonin-1, with 91 and 75% identity at the amino acid level, respectively. The numbers of immunoglobulin (IgC2) domains and fibronectin repeats present in TAG-1 are conserved among the three species. The highest degree of conservation occurs in the second IgC2 domain (98% with the rat and 82% with the chick). The human homologue also contains a putative N-terminal signal sequence and a C-terminal hydrophobic sequence, suggestive of linkage to the cell membrane via phosphatidylinositol. In addition, the two mammalian TAG-1 proteins share the RGD tripeptide, a motif known to mediate recognition of fibronectin by integrins. In situ hybridization to human metaphase chromosomes maps the TAX1 gene encoding human TAG-1 to a single location on chromosome 1q32.

Asunto(s)

Moléculas de Adhesión Celular Neuronal , Cerebelo/metabolismo , Cromosomas Humanos Par 1 , ADN Complementario/aislamiento & purificación , Hominidae/genética , Glicoproteínas de Membrana/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Pollos/genética , Mapeo Cromosómico , Secuencia Conservada , Contactina 2 , Cartilla de ADN , Fibronectinas/genética , Genes de Inmunoglobulinas , Humanos , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Ratas/genética , Homología de Secuencia de Aminoácido