http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc#Head http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc http://www.nanopub.org/nschema#hasAssertion http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc#assertion http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc http://www.nanopub.org/nschema#hasProvenance http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc#provenance http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc http://www.nanopub.org/nschema#hasPublicationInfo http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc#pubinfo http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc http://www.w3.org/1999/02/22-rdf-syntax-ns#type http://www.nanopub.org/nschema#Nanopublication http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc#assertion http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc#_1 http://purl.obolibrary.org/obo/BFO_0000066 http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=10090 http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc#_1 http://www.w3.org/1999/02/22-rdf-syntax-ns#object http://purl.bioontology.org/ontology/MSH/D007333 http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc#_1 http://www.w3.org/1999/02/22-rdf-syntax-ns#predicate http://www.selventa.com/vocabulary/increases http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc#_1 http://www.w3.org/1999/02/22-rdf-syntax-ns#subject http://www.ebi.ac.uk/chebi/searchId.do?chebiId=7242 http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc#_1 http://www.w3.org/1999/02/22-rdf-syntax-ns#type http://www.w3.org/1999/02/22-rdf-syntax-ns#Statement http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc#assertion http://www.w3.org/2000/01/rdf-schema#label a(CHEBI:ceramide) -> bp(MESHPP:"Insulin Resistance") http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc#provenance http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/description Approximately 61,000 statements. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/rights Copyright (c) 2011-2012, Selventa. All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc#_3 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc#_2 http://www.w3.org/ns/prov#value Recent studies indicate that insulin resistance and type 2 diabetes result from the accumulation of lipids in tissues not suited for fat storage, such as skeletal muscle and the liver. To elucidate the mechanisms linking exogenous fats to the inhibition of insulin action, we evaluated the effects of free fatty acids (FFAs) on insulin signal transduction in cultured C2C12 myotubes. As we described previously (Chavez, J. A., and Summers, S. A. (2003) Arch. Biochem. Biophys. 419, 101-109), long-chain saturated FFAs inhibited insulin stimulation of Akt/protein kinase B, a central regulator of glucose uptake and anabolic metabolism. Moreover, these FFAs stimulated the de novo synthesis of ceramide and sphingosine, two sphingolipids shown previously to inhibit insulin action. To determine the contribution of either sphingolipid in FFA-dependent inhibition of insulin action, we generated C2C12 myotubes that constitutively overexpress acid ceramidase (AC), an enzyme that catalyzes the lysosomal conversion of ceramide to sphingosine. AC overexpression negated the inhibitory effects of saturated FFAs on insulin signaling while blocking their stimulation of ceramide accumulation. By contrast, AC overexpression stimulated the accrual of sphingosine. These results support a role for aberrant accumulation of ceramide, but not sphingosine, in the inhibition of muscle insulin sensitivity by exogenous FFAs. Moreover, these FFAs stimulated the de novo synthesis of ceramide and sphingosine, two sphingolipids shown previously to inhibit insulin action. http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc#_2 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/15774472 http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc#_3 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/15774472 http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc#_2 http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc#pubinfo http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc http://purl.org/dc/terms/created 2014-07-03T14:30:33.464+02:00 http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAoKURMmBKSLjLEW0yB38SC9LmsuBZJDQVd0EstBGcWvc http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234