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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/RA0BG_sE_qvAA1XVluPbpVNvQSZURRHaz4nSQHByUUit0#_4 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RA0BG_sE_qvAA1XVluPbpVNvQSZURRHaz4nSQHByUUit0#_3 http://www.w3.org/ns/prov#value The significance of endogenous visfatin controlling whole-body insulin sensitivity is reinforced by the phenotype of lean, heterozygous visfatin-knockout mice, which revealed mild but reproducible hyperglycaemia. Subsequent analysis of this insulin-mimetic effect revealed two surprising findings: that the effects of visfatin are mediated by the insulin receptor itself, with remarkably similar affinities to those of insulin but through a distinct binding site, and that this insulin-sensitizing effect of visfatin might be additive to the effect of insulin, suggesting that visfatin activates insulin-receptor-activated pathways through a novel mechanism. What is the physiological relevance of visfatin for the metabolic syndrome? The discovery of this curious new adipokine has great potential to significantly enhance our understanding of the metabolic syndrome. However, as with most new discoveries, these findings need to be reproduced. Indeed, there is already an indication that the correlation between visfatin gene expression and the metabolic syndromemight not be universal to all models [8]. Novel findings also raise several newquestions that need to be addressed before their true significance can be appreciated. It will be necessary to determine the contribution of visfatin originating from visceral adipose tissue to the control of global insulin sensitivity. Although the affinity of visfatin for the insulin receptor appears to be similar to insulin, its concentration in plasma is much lower (3-10% of the insulin concentration) under physiological conditions. It is also not regulated by fasting and feeding. This raises doubts about the physiological importance of the systemic insulinsensitizing effects of visfatin. However, the dramatic elevation of visfatin levels in the visceral adipose tissue of obese mice suggests that it has a significant role in the pathophysiology of obesity. http://www.tkuhn.ch/bel2nanopub/RA0BG_sE_qvAA1XVluPbpVNvQSZURRHaz4nSQHByUUit0#_3 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/16005682 http://www.tkuhn.ch/bel2nanopub/RA0BG_sE_qvAA1XVluPbpVNvQSZURRHaz4nSQHByUUit0#_4 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RA0BG_sE_qvAA1XVluPbpVNvQSZURRHaz4nSQHByUUit0#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/16005682 http://www.tkuhn.ch/bel2nanopub/RA0BG_sE_qvAA1XVluPbpVNvQSZURRHaz4nSQHByUUit0#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RA0BG_sE_qvAA1XVluPbpVNvQSZURRHaz4nSQHByUUit0#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RA0BG_sE_qvAA1XVluPbpVNvQSZURRHaz4nSQHByUUit0#_3 http://www.tkuhn.ch/bel2nanopub/RA0BG_sE_qvAA1XVluPbpVNvQSZURRHaz4nSQHByUUit0#pubinfo http://www.tkuhn.ch/bel2nanopub/RA0BG_sE_qvAA1XVluPbpVNvQSZURRHaz4nSQHByUUit0 http://purl.org/dc/terms/created 2014-07-03T14:30:36.518+02:00 http://www.tkuhn.ch/bel2nanopub/RA0BG_sE_qvAA1XVluPbpVNvQSZURRHaz4nSQHByUUit0 http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RA0BG_sE_qvAA1XVluPbpVNvQSZURRHaz4nSQHByUUit0 http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234