Mitochondrial fragmentation impairs insulin-dependent glucose uptake by modulating Akt activity through mitochondrial Ca2+ uptake

Andrea del Campo, Valentina Parra, César Vásquez-Trincado, Tomás Gutiérrez, Pablo E. Morales, Camila López-Crisosto, Roberto Bravo-Sagua, Mario F. Navarro-Marquez, Hugo E. Verdejo, Ariel Contreras-Ferrat, Rodrigo Troncoso, Mario Chiong, Sergio Lavandero

Resultado de la investigación: Contribución a una revistaArtículo

34 Citas (Scopus)

Resumen

Insulin is a major regulator of glucose metabolism, stimulating its mitochondrial oxidation in skeletal muscle cells. Mitochondria are dynamic organelles that can undergo structural remodeling in order to cope with these everchanging metabolic demands. However, the process by which mitochondrial morphology impacts insulin signaling in the skeletal muscle cells remains uncertain. To address this question, we silenced the mitochondrial fusion proteins Mfn2 and Opa1 and assessed insulin-dependent responses in L6 rat skeletal muscle cells. We found that mitochondrial fragmentation attenuates insulin-stimulated Akt phosphorylation, glucose uptake and cell respiratory rate. Importantly, we found that insulin induces a transient rise in mitochondrial Ca2+ uptake, which was attenuated by silencing Opa1 or Mfn2. Moreover, treatment with Ruthenium red, an inhibitor of mitochondrial Ca2+ uptake, impairs Akt signaling without affecting mitochondrial dynamics. All together, these results suggest that control of mitochondrial Ca2+ uptake by mitochondrial morphology is a key event for insulininduced glucose uptake.

Idioma originalInglés
Páginas (desde-hasta)E1-E13
PublicaciónAmerican Journal of Physiology - Endocrinology and Metabolism
Volumen306
N.º1
DOI
EstadoPublicada - 1 ene 2014
Publicado de forma externa

Áreas temáticas de ASJC Scopus

  • Endocrinología, diabetes y metabolismo
  • Fisiología
  • Fisiología (médica)

Huella Profundice en los temas de investigación de 'Mitochondrial fragmentation impairs insulin-dependent glucose uptake by modulating Akt activity through mitochondrial Ca<sup>2+</sup> uptake'. En conjunto forman una huella única.

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    del Campo, A., Parra, V., Vásquez-Trincado, C., Gutiérrez, T., Morales, P. E., López-Crisosto, C., Bravo-Sagua, R., Navarro-Marquez, M. F., Verdejo, H. E., Contreras-Ferrat, A., Troncoso, R., Chiong, M., & Lavandero, S. (2014). Mitochondrial fragmentation impairs insulin-dependent glucose uptake by modulating Akt activity through mitochondrial Ca2+ uptake. American Journal of Physiology - Endocrinology and Metabolism, 306(1), E1-E13. https://doi.org/10.1152/ajpendo.00146.2013