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

Authors: del Campo, Andrea  Parra, Valentina  Vásquez-Trincado, César  Gutiérrez, Tomás  Morales, Pablo E  López-Crisosto, Camila  Bravo-Sagua, Roberto  Navarro-Marquez, Mario F  Verdejo, Hugo E  Contreras-Ferrat, Ariel  Troncoso, Rodrigo  Chiong, Mario  Lavandero, Sergio 
Citation: del Campo A, etal., Am J Physiol Endocrinol Metab. 2014 Jan 1;306(1):E1-E13. doi: 10.1152/ajpendo.00146.2013. Epub 2013 Oct 1.
Pubmed: (View Article at PubMed) PMID:24085037
DOI: Full-text: DOI:10.1152/ajpendo.00146.2013

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 ever-changing 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 Ca(2+) uptake, which was attenuated by silencing Opa1 or Mfn2. Moreover, treatment with Ruthenium red, an inhibitor of mitochondrial Ca(2+) uptake, impairs Akt signaling without affecting mitochondrial dynamics. All together, these results suggest that control of mitochondrial Ca(2+) uptake by mitochondrial morphology is a key event for insulin-induced glucose uptake.

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CRRD Object Information
CRRD ID: 13208948
Created: 2017-08-24
Species: All species
Last Modified: 2017-08-24
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.