Cookies help us deliver our services. By using our services, you agree to our use of cookies. More information

Contreras-Ferrat 2014 Abstract MiP2014

From Bioblast
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.

Link: MiP2014, Book of Abstracts Open Access

Contreras-Ferrat A, Llanos P, Meza C, Utreras Y, Diaz A, Arias M, Jaimovich E (2014)

Event: MiP2014

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 [1]. 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 [4].

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 

Affiliation

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.

  1. Berridge MJ (1997) Elementary and global aspects of calcium signalling. J Physiol 499: 291-306.
  2. Lessard SJ, Rivas DA, Chen ZP, Bonen A, Febbraio MA, Reeder DW (2007) Tissue specific effects of rosiglitazone and exercise in the treatment of lipid-induced insulin resistance. Diabetes 56:1856-64.
  3. Yaspelkis BB, Lessard SJ, Reeder DW, Limon JJ, Saito M, Rivas DA (2007) Exercise reverses high-fat diet-induced impairments on compartmentalization and activation of components of the insulin-signaling cascade in skeletal muscle. Am J Physiol Endocrinol Metab 293: E941-9.
  4. Bell JA, Reed MA, Consitt LA, Martin OJ, Haynie KR, Hulver MW (2010) Lipid partitioning, incomplete fatty acid oxidation, and insulin signal transduction in primary human muscle cells: effects of severe obesity, fatty acid incubation, and fatty acid translocase/CD36 overexpression. J Clin Endocrinol Metab 95: 3400-10.