Mitochondrial fragmentation impairs insulin-dependent glucose uptake by modulating Akt activity through mitochondrial Ca2+ uptake
Author
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Del Campo, Andrea
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Parra, Valentina
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Vásquez Trincado, César Alonso
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Gutiérrez, Tomás
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Morales, Pablo E.
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López Crisosto, Camila
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Bravo Sagua, Roberto
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Navarro Márquez, Mario F.
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Verdejo, Hugo E.
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Contreras Ferrat, Ariel Eduardo
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Troncoso, Rodrigo
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Chiong Lay, Mario
Author
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Lavandero González, Sergio
Admission date
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2019-03-15T16:05:48Z
Available date
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2019-03-15T16:05:48Z
Publication date
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2014
Cita de ítem
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American Journal of Physiology - Endocrinology and Metabolism, Volumen 306, Issue 1, 2018,
Identifier
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01931849
Identifier
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15221555
Identifier
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10.1152/ajpendo.00146.2013
Identifier
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https://repositorio.uchile.cl/handle/2250/166061
Abstract
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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 th