Contreras-Ferrat 2014 Abstract MiP2014
|Insulin increases mitochondrial calcium levels regulating both mitochondrial function and intracellular signaling in muscle; this effect is disrupted in fibers from short-term high fat diet fed mice. Mitochondr Physiol Network 19.13.|
Mitochondrial function rapidly responds to high energy food supply in order to deal with the supply, but the role of mitochondrial Ca2+ in these processes is not yet understood . High-fat fed mice quickly gain weight while concomitantly developing insulin resistance in skeletal muscle [2,3]. For obesity, inappropriate lipid deposition in human skeletal muscle and a concomitant reduction in the ability of cells to completely oxidize lipids have been described .
Male C57BL/6J mice were fed either a normal chow diet (NCD) or a high fat diet (HFD) for one or eight weeks. Insulin resistance was evaluated by IPGTT, fasting glucose and insulin, and HOMA-IR. GLUT4myc-eGFP was electroporated in the Flexor digitorum brevis muscle (FDB). Insulin induces an increase in cytoplasmic and mitochondrial Ca2+ in adult fibers. The uncoupler FCCP releases Ca2+ from mitochondria to cytoplasm. Insulin-dependent mitochondrial Ca2+ uptake is decreased in fibers from short-term HFD fed mice, while insulin-dependent cytoplasmic Ca2+ increase appear to be faster and stronger. In fibers from NCD fed mice, insulin-dependent mitochondrial Ca2+ uptake was inhibited by xestospongin B, a specific inhibitor of inositol-1,4,5-trisphosphate receptor. Using TMRE+ in the non-quenching mode (5 nM), we found that ΔΨmt was larger in fibers from short-term HFD fed mice in comparison to NCD derived fibers. Using TMRE+ in quenching mode (100 nM), we found that TMRE+, released after uncoupler stimuli, was higher in fibers from short-term HFD fed mice than in NCD fed mice. The glucose analogue (2-NBDG) uptake and the redistribution of GLUT4myceGFP, induced by insulin, were decreased in the presence of xestospongin or ruthenium red (MCU inhibitor). This effect suggests a retrograde regulation of insulin signaling by mitochondrial Ca2+ uptake.
Labels: MiParea: Exercise physiology;nutrition;life style Pathology: Diabetes
Organism: Mouse Tissue;cell: Skeletal muscle Preparation: Intact cells
Regulation: Calcium, Uncoupler
Event: C3, Oral MiP2014
1-Center Molec Studies of the Cell, Fac Medicina; 2-Inst Research Dental Sc, Fac Odontología, Univ Chile; Santiago, Chile. - [email protected]
References and acknowledgements
Financed by FONDECYT 11130267, ACT1111.
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