Muscle wasting is a serious complication of various clinical conditions that significantly worsens the prognosis of the illnesses. Clinically relevant models of muscle wasting are essential for understanding its pathogenesis and for selective preclinical testing of potential therapeutic agents. The data presented here indicate that muscle wasting has been well characterized in rat models of sepsis (endotoxaemia, and caecal ligation and puncture), in rat models of chronic renal failure (partial nephrectomy), in animal models of intensive care unit patients (corticosteroid treatment combined with peripheral denervation or with administration of neuromuscular blocking drugs) and in murine and rat models of cancer (tumour cell transplantation). There is a need to explore genetically engineered mouse models of cancer. The degree of protein degradation in skeletal muscle is not well characterized in animal models of liver cirrhosis, chronic heart failure and chronic obstructive pulmonary disease. The major difficulties with all models are standardization and high variation in disease progression and a lack of reflection of clinical reality in some of the models. The translation of the information obtained by using these models to clinical practice may be problematic.
- MeSH
- kosterní svaly metabolismus patologie MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- nádory komplikace metabolismus patologie MeSH
- proteolýza MeSH
- sepse komplikace metabolismus patologie MeSH
- svalová atrofie etiologie metabolismus patologie MeSH
- syndrom chřadnutí etiologie metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Extracellular adenosine is an important signaling molecule in neuromodulation, immunomodulation and hypoxia. Adenosine dysregulation can cause various pathologies, exemplified by a deficiency in adenosine deaminase in severe combined immunodeficiency. We have established a Drosophila model to study the effects of increased adenosine in vivo by mutating the main Drosophila adenosine deaminase-related growth factor (ADGF-A). Using a genetic screen, we show here that the increased extracellular adenosine in the adgf-a mutant is associated with hyperglycemia and impairment in energy storage. The adenosine works in this regard through the adenosine receptor as an anti-insulin hormone in parallel to adipokinetic hormone, a glucagon counterpart in flies. If not regulated properly, this action can lead to a loss of energy reserves (wasting) and death of the organism. Because adenosine signaling is associated with the immune response and the response to stress in general, our results mark extracellular adenosine as a good candidate signal involved in the wasting syndrome that accompanies various human pathologies.
- MeSH
- adenosin metabolismus MeSH
- adipokiny metabolismus MeSH
- dieta MeSH
- Drosophila melanogaster enzymologie MeSH
- energetický metabolismus MeSH
- extracelulární prostor metabolismus MeSH
- fenotyp MeSH
- fosforylasakinasa genetika metabolismus MeSH
- hemolymfa metabolismus MeSH
- kalorická restrikce MeSH
- larva metabolismus MeSH
- mutace genetika MeSH
- proteiny Drosophily nedostatek genetika metabolismus MeSH
- purinergní receptory P1 metabolismus MeSH
- sacharidy krev MeSH
- signální transdukce MeSH
- suprese genetická MeSH
- syndrom chřadnutí enzymologie patologie MeSH
- tukové těleso metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH