Proceedings of The Physiological Society

University of Cambridge (2008) Proc Physiol Soc 11, C111

Oral Communications

Low glucose availability induces metabolic transformation of primary rabbit muscle cells in culture

H. Kubis1, J. D. Meissner2, R. J. Scheibe2, V. Endeward2, G. Gros2, N. Hanke2

1. School of Sport, Health and Exercise Sciences, Bangor University, Bangor, United Kingdom. 2. Zentrum Physiologie, Medical School Hanover, Hanover, Germany.

Adult skeletal muscle cells are differentiated into various fibre types with distinct mechanical and biochemical properties. Nevertheless skeletal muscle fibres reveal an enormous potential to adapt to chronic physical load by an alteration of metabolic capacity and contractile properties up to a complete transformation of fibre type. Using primary skeletal muscles grown on microcarriers we could show that the transformation of fast to slow myosin depends on the signalling cascade calcium-calmodulin-calcineurin-NFATc1. However, the regulation of metabolic adaptation to exercise and chronic electrical stimulation seems not to be solely linked to calcium signalling and not to calcineurin activation. Therefore we investigated possible further mechanisms which might be involved in metabolic transformation typically associated with fast-to-slow transition of fibre type in rabbit skeletal muscle cells. We hypothesized that lowered intracellular ATP concentration or reduction of the glycogen stores could act as triggers of metabolic transformation. Three days of pharmacological reduction of cytosolic ATP concentration by 5 mM 3-guanidino propionic acid had no impact on the investigated metabolic markers, whereas incubation of the cells with little or no glucose leads to decreases in glycogen in conjunction with decreases in glyceraldehyde-3-phosphate dehydrogenase (GAPDH) promoter activity, GAPDH mRNA and specific GAPDH enzyme activity (indicators of the anaerobic glycolytic pathway). Furthermore, reduction of glucose availability increased promoter activity of mitochondrial acetoacetyl-CoA thiolase (MAT, also known as ACAT), mRNA expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and citrate synthase (CS) specific enzyme activity (all indicators of oxidative metabolic pathways). In experiments with two inhibitors of glycogen degradation 1,4-dideoxy-1,4-D-arabinitol (DAB, Novo Nordisk, Bagsvaerd, Denmark) or N-Butyldeoxynojirimycin (BDN, Calbiochem/Merck, Darmstadt, Germany) we found that the observed metabolic transformation caused by low glucose was induced even when intracellular glycogen content was high. These findings provide evidence that metabolic adaptation of skeletal muscle cells from rabbit in primary culture can be induced not only by elevation of intracellular calcium concentration or by a rise of AMPK activity, but also by reduction of glucose availability.

Where applicable, experiments conform with Society ethical requirements