RGD Reference Report - Rapamycin-mediated inhibition of mammalian target of rapamycin in skeletal muscle cells reduces glucose utilization and increases fatty acid oxidation. - Rat Genome Database

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Rapamycin-mediated inhibition of mammalian target of rapamycin in skeletal muscle cells reduces glucose utilization and increases fatty acid oxidation.

Authors: Sipula, IJ  Brown, NF  Perdomo, G 
Citation: Sipula IJ, etal., Metabolism. 2006 Dec;55(12):1637-44.
RGD ID: 1625611
Pubmed: PMID:17142137   (View Abstract at PubMed)
DOI: DOI:10.1016/j.metabol.2006.08.002   (Journal Full-text)

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays an important role in cell growth and metabolism. mTOR has been postulated as a nutrient sensor, but its role in the regulation of fatty acid and glucose metabolism is poorly understood. For the first time, we show that mTOR inhibition in skeletal muscle cells has pronounced effects on intermediary metabolism. Rapamycin, a uniquely specific mTOR inhibitor with clinical applications, increased fatty acid oxidation by 60% accompanied by increased activities of carnitine palmitoyltransferases I and II, the former believed to be the primary intracellular regulatory enzyme of the fatty acid oxidation pathway. Furthermore, glucose transport capacity, glycogen synthesis, and glycolysis were reduced by approximately 40% under the same conditions. In addition, in the presence of rapamycin, hyperinsulinemic conditions (100 nmol/L insulin, 24 hours) were unable to suppress fatty acid oxidation in L6 myotubes. Rapamycin treatment also decreased baseline phosphorylation of mTOR residues S2448 and S2481 by 30% and almost completely abolished p70 S6 kinase phosphorylation. These results show that rapamycin causes a metabolic shift from glucose utilization to fatty acid oxidation in model muscle cells in the presence of nutrient abundance and underline the importance of mTOR as a key regulator in glucose and lipid metabolism.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MtorRatprotein serine/threonine kinase activity  IDA  RGD 
MtorRatprotein serine/threonine kinase activity  IMP  RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MTORHumanmTOR signaling pathway   ISOMtor (Rattus norvegicus) RGD 
MtorRatmTOR signaling pathway   IDA  RGD 
MtorRatmTOR signaling pathway   IMP  RGD 
MtorMousemTOR signaling pathway   ISOMtor (Rattus norvegicus) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Mtor  (mechanistic target of rapamycin kinase)

Genes (Mus musculus)
Mtor  (mechanistic target of rapamycin kinase)

Genes (Homo sapiens)
MTOR  (mechanistic target of rapamycin kinase)


Additional Information