EFECTO PROTECTOR DEL VALSARTAN EN LA RESISTENCIA NEURONAL A LA INSULINA Y LA INFLAMACION EN LA DIABETES TIPO 2




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EFECTO PROTECTOR DEL VALSARTAN EN LA RESISTENCIA NEURONAL A LA INSULINA Y LA INFLAMACION EN LA DIABETES TIPO 2

(especial para SIIC © Derechos reservados)
La evidencia sugiere que la diabetes tipo 2 no sólo es un trastorno metabólico con consecuencias en el sistema nervioso, sino también un trastorno del sistema nervioso con consecuencias metabólicas e inflamatorias. El uso de agentes que inhiben las acciones de la angiotensina II, como el valsartán, parecen ejercer un importante efecto protector en el mantenimiento de la comunicación entre los circuitos hipotalámicos relacionados con el mantenimiento del balance energético y la periferia.
Autor:
Mariella Pastorello
Columnista Experta de SIIC

Institución:
Laboratorio de Neuropeptidos, Facultad de Farmacia, Universidad Central de Venezuela


Artículos publicados por Mariella Pastorello
Coautor
Anita Israel* 
Farmaceutico, Universidad Central de Venezuela, Caracas, Venezuela*

Resumen
Introducción: La diabetes mellitus tipo 2 (DBT2) se asocia con alteraciones de los mecanismos contrarregulatorios ejercidos por la insulina a nivel del sistema nervioso central (SNC). Existe evidencia de que los receptores de insulina y AT1 de la angiotensina II están colocalizados en el hipotálamo, lo que sugiere la interacción de estos dos péptidos en el SNC. En la periferia, la angiotensina II promueve estrés oxidativo, resistencia a la insulina y nefropatía diabética; sin embargo, poco se sabe acerca de si los efectos deletéreos se manifiestan a nivel del SNC en la DBT2. Por ello, evaluamos el efecto de la angiotensina II sobre las acciones de la insulina central en ratas controles y con diabetes inducida por estreptozotocina. Igualmente, se estudió el posible efecto protector central y antiinflamatorio sistémico del valsartán. Materiales y métodos: El estado inflamatorio sistémico se evaluó mediante el análisis multiplex de microesferas. La resistencia neuronal a la insulina se determinó mediante la cuantificación de la glucemia en ratas tratadas en forma intracerebroventricular (ICV) con angiotensina II, con insulina o con ambas, pretratadas o no con valsartán. Resultados: Se demuestra que la insulina ICV ejerce un efecto hipoglucemiante, cuya magnitud es menor en condiciones diabéticas. La angiotensina II central antagonizó los efectos hipoglucemiantes de la insulina ICV. El valsartán previno la resistencia neuronal a la insulina, bloqueó las acciones de la angiotensina II ICV y redujo los niveles circulantes de citoquinas proinflamatorias. Conclusiones: Los resultados demuestran que existe resistencia neuronal a la insulina y un estado proinflamatorio sistémico en la DBT2 experimental, los cuales son evitados parcialmente por el valsartán.

Palabras clave
angiotensina, insulina, valsartán, diabetes, hipotálamo, resistencia neuronal, inflamación


Artículo completo

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Abstract
Introduction: Diabetes mellitus type 2 (DBT2) is associated with alterations of counter-regulatory mechanisms exerted by insulin in the central nervous system. There is evidence that insulin receptor and AT1 angiotensin-II receptor are co-localized in the hypothalamus, suggesting an interaction of these two peptides in the central nervous system. On the periphery, angiotensin-II promotes oxidative stress, insulin resistance and the development of diabetic nephropathy; however, little is known whether the deleterious effects are manifested at central nervous system in DBT2. Therefore, we evaluated the effect of angiotensin-II on central insulin actions in control and streptozotocin-induced diabetic rats. Similarly, the possible central protective effect and systemic anti-inflammatory action of valsartan was studied. Materials and methods: The systemic inflammatory status was assessed by multiplex bead analysis. Neuronal insulin resistance was determined by quantification of glycemia in rats after intracerebroventricularly (ICV) administration of angiotensin-II and/or insulin, pretreated or not with valsartan. Results: It is shown that ICV administration of insulin exerts a hypoglycemic effect, whose magnitude is lower in diabetic conditions. Meanwhile central administration of angiotensin-II antagonized the hypoglycemic effects of insulin-ICV. Valsartan prevented neuronal insulin resistance, blocked the action of angiotensin-II-ICV and reduced circulating levels of pro-inflammatory cytokines. Conclusions: The results show that there is neuronal insulin resistance and systemic pro-inflammatory state in the experimental DBT2, which are partially prevented by chronic treatment with valsartan.

Key words
angiotensin, insulin, valsartan, diabetes, hypothalamus, neuronal resistance, inflammation


Clasificación en siicsalud
Artículos originales > Expertos de Iberoamérica >
página   www.siicsalud.com/des/expertocompleto.php/

Especialidades
Principal: Diabetología, Farmacología
Relacionadas: Cardiología, Endocrinología y Metabolismo, Inmunología



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