EL AGONISTA SINTETICO DEL RECEPTOR GAMMA ACTIVADO POR PROLIFERADOR DE PEROXISOMAS, ROSIGLITAZONA, AUMENTA LOS NIVELES PLASMATICOS DE ADIPONECTINA EN PACIENTES CON DIABETES TIPO 2: CONSECUENCIAS CLINICAS

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La rosiglitazona eleva en más de dos veces el nivel promedio de adiponectina en plasma. El tratamiento con rosiglitazona parece ser el único parámetro relacionado en forma independiente con las modificaciones en la adiponectina plasmática.
chuang.jpg Autor:
Lee-ming Chuang
Columnista Experto de SIIC
Artículos publicados por Lee-ming Chuang
Recepción del artículo
28 de Noviembre, 2003
Primera edición
30 de Abril, 2004
Segunda edición, ampliada y corregida
7 de Junio, 2021

Resumen
La adiponectina, una citoquina de adipocitos, tiene propiedades antiinflamatorias y antiaterogénicas. La administración de adiponectina a animales se asocia con reducción de la glucosa plasmática y aumento de la sensibilidad a la insulina. En el hombre, la concentración plasmática de adiponectina se ha relacionado con los principales componentes del síndrome metabólico. El receptor γ activado por proliferador de peroxisomas (PPAR)-γ es un factor transcripcional crucial que controla muchos genes de adipocitos. Investigamos si el nivel de adiponectina podía elevarse con el tratamiento con el agonista del PPAR-γ -rosiglitazona- en pacientes con diabetes tipo 2 reclutados para un estudio aleatorizado a doble ciego y controlado con placebo. El nivel promedio de adiponectina aumentó más dos veces (P = 0.0005) en el grupo asignado a rosiglitazona mientras que no se observaron cambios en el grupo placebo. El análisis de regresión lineal de multivariado mostró que el tratamiento con rosiglitazona fue el único parámetro relacionado en forma significativa con las modificaciones en la adiponectina plasmática. La terapia contribuyó con el 24% de la variabilidad en la concentración sérica de adiponectina luego del control de otros factores de confusión. En un estudio genético en una amplia cohorte de familias hipertensas, encontramos que el polimorfismo del gen de adiponectina se asocia con la sensibilidad a la insulina. El efecto de la adiponectina se modifica acorde a los genotipos PPAR-γ2, lo cual indica una interacción genética en la sensibilidad a la insulina. Estas observaciones sugieren que la mayor expresión de adiponectina puede contribuir con los beneficios anti-hiperglucémicos y posiblemente antiaterogénicos de los agonistas del PPAR-&gamma.


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Abstract
Adiponectin, an adipocytokine, exhibits anti-inflammatory and anti-atherogenic properties. Administration of adiponectin to animals reduces plasma glucose and increased insulin sensitivity. In human subjects, plasma levels of adiponectin have been linked with major components of metabolic syndrome. The peroxisome proliferators-activated receptor (PPAR)-γ is a key transcriptional factor that controls many adipocyte genes. We investigated whether the level of adiponectin could be increased by treatment with a PPAR-γ agonist, rosiglitazone, in type 2 diabetes patients recruited for a randomized double-blind placebo-controlled trial. The mean plasma adiponectin level was increased by more than twofold (P<0.0005) in the rosiglitazone group, whereas no change was observed in the placebo group. Multivariate linear regression analysis showed that rosiglitazone treatment was the single variable significantly related to the changes of plasma adiponectin. The treatment contributed to 24% of the variance in changes of plasma adiponectin after adjusting for other factors. In a genetic study based on a large hypertensive family cohort, we found that adiponectin gene polymorphism was associated with insulin sensitivity. The effect of adiponectin was modified by PPARγ2 genotypes, indicating a genetic interaction in insulin sensitivity. These observations suggest that increased adiponectin expression may contribute to the anti-hyperglycemic and putative anti-atherogenic benefits of PPAR-γ agonists.


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Especialidades
Principal: Endocrinología y Metabolismo
Relacionadas: Bioquímica, Farmacología, Medicina Farmacéutica



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