Linked Life Data

17925406

Source:http://linkedlifedata.com/resource/pubmed/id/17925406

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
48
pubmed:dateCreated
2007-11-26
pubmed:abstractText
Recently, single chain peptides have been designed that target the insulin receptor and mimic insulin action. The aim of this study is to explore if activation of the insulin receptor with such an optimized peptide (S597) leads to the same activation of signaling pathways and biological endpoints i.e. stimulation of glycogen synthesis and cell proliferation as stimulation with insulin. We find that surface activation of the insulin receptor A-isoform with S597 leads to activation of protein kinase B (PKB) and glycogen synthesis comparable to activation by insulin, even though the level of insulin receptor phosphorylation is lower. In contrast, both Src homology 2/alpha collagen-related (Shc) and extracellular signal-regulated kinase (ERK) 2 activation are virtually absent upon stimulation with S597. Cell proliferation is only stimulated slightly by S597, suggesting that it depends on signals from Shc and ERK. The differences in signaling response could explain both the earlier reported differences in gene expression, and the reported differences in cell proliferation and glycogen synthesis induced by insulin and S597. In conclusion, despite binding equipotency, insulin, and S597 initiate different signaling and biological responses through the same insulin receptor isoform. We show for the first time that it is possible to design insulin receptor ligand mimetics with metabolic equipotency but low mitogenicity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35179-86
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Activation of the insulin receptor by insulin and a synthetic peptide leads to divergent metabolic and mitogenic signaling and responses.
pubmed:affiliation
Receptor Systems Biology Laboratory, Hagedorn Research Institute, 2820 Gentofte, Denmark. mjjn@novonordisk.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't