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El receptor contrarresta la señalización de la insulina en las células β para controlar la glucemia
Ansarullah1,2, Chirag Jain1,2, Fataneh Fathi Far1,3
1Institute of Diabetes and Regeneration Research, Helmholtz Center Munich, Neuherberg, Germany.
Nature
|January 28, 2021
Resumen
Los investigadores descubrieron una nueva proteína, el inceptor, que regula la señalización de la insulina en las células beta del páncreas. El bloqueo del inceptor aumenta la actividad de los receptores de insulina, ofreciendo potencialmente un nuevo objetivo terapéutico para el tratamiento de la diabetes.
Área de la Ciencia:
- Endocrinología
- Biología molecular
- Biología celular
Sus antecedentes:
- La resistencia a la insulina y al IGF1 en las células beta del páncreas conduce a la diabetes.
- Las terapias que sensibilizan a las células beta a la insulina pueden prevenir la insuficiencia de las células beta.
- Comprender la señalización de las células beta es crucial para el manejo de la diabetes.
Objetivo del estudio:
- Identificar nuevos reguladores de la señalización de la insulina y del receptor IGF1 en las células beta pancreáticas.
- Investigar el papel del receptor inhibidor de la insulina (inceptor) en la función y el desarrollo de las células beta.
- Para explorar el inceptor como un objetivo terapéutico potencial para la diabetes.
Principales métodos:
- Generación y análisis de ratones noqueadores receptores.
- Análisis moleculares y celulares de tejidos pancreáticos y islotes aislados.
- Evaluación de la activación y señalización del receptor de insulina (INSR) y del receptor de IGF1 (IGF1R).
- Estudios in vivo de la tolerancia a la glucosa y la proliferación de las células beta.
- Uso de anticuerpos monoclonales para bloquear las interacciones receptor-inceptor.
Principales resultados:
- Los ratones knockout receptores presentan hiperinsulinemia severa, hipoglucemia y letalidad perinatal.
- La pérdida del receptor conduce a un aumento de la activación del INSR-IGF1R, la proliferación de las células beta y la masa.
- El knockout inducible del inceptor específico de células beta mejora la tolerancia a la glucosa y la proliferación de células beta en ratones adultos.
- El receptor facilita la endocitosis mediada por clatrina para la desensibilización del INSR-IGF1R.
- El bloqueo de la interacción inceptor-receptor mantiene la activación de INSR-IGF1R en las células beta.
Conclusiones:
- El receptor actúa como un regulador negativo crucial, protegiendo las células beta pancreáticas de la insulina constitutiva y la señalización de IGF1.
- El receptor protege a las células beta de la activación excesiva, evitando el fallo potencial.
- Inceptor es un objetivo molecular prometedor para el desarrollo de terapias para sensibilizar a las células beta y tratar la diabetes.
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