Linked Life Data

11932207

Source:http://linkedlifedata.com/resource/pubmed/id/11932207

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-4-4
pubmed:abstractText
We investigated the role of hepatocyte growth factor (HGF) in beta-cell growth and its complex intracellular signal transduction pathways. Cell proliferation was measured in the beta-cell line INS-1 using [3H]thymidine incorporation. Activation of mitogenic signaling proteins was assessed using co-immunoprecipitation, immunoblot analysis and specific protein activity inhibitors in proliferation assays. HGF (1 x 375 nM) increased INS-1 cell proliferation in the presence of 3-24 mM glucose up to 45-fold vs unstimulated controls. HGF exceeded the effect of glucose alone (2 x 2-fold at 3 mM glucose and 1 x 7-fold in the presence of 15 mM glucose). The HGF-induced INS-1 cell proliferation was further increased by addition of IGF-I or GH. Stimulation with HGF activated the JAK-2/STAT-5 pathway with a subsequent activation of phosphatidylinositol-3'-kinase (PI3'K). PI3'K activation was necessary for HGF- and glucose-stimulated INS-1 cell proliferation. The effect of PI3'K was mediated via 70 kDa S6 kinase and protein kinase B, which showed maximum activation in the presence of 3-6 mM glucose. Protein kinase C was essential for HGF-induced INS-1 cell proliferation. The HGF effect was also mediated at low glucose concentrations via insulin receptor substrate 4 (IRS-4) whereas other IRS proteins did not show any activation. High glucose concentrations also showed an increased IRS-4/PI3'K binding and therefore activation. In conclusion, beta-cell proliferation is mediated via complex interacting signal transduction pathways. HGF, in contrast to other growth factors, seems to be of importance particularly in the presence of low glucose concentrations and therefore takes a special role in this complex concert.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0952-5041
pubmed:author
pubmed:issnType
Print
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
99-110
pubmed:dateRevised
2002-11-1
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Hepatocyte growth factor stimulates proliferation of pancreatic beta-cells particularly in the presence of subphysiological glucose concentrations.
pubmed:affiliation
Department of Internal Medicine I, University of Regensburg, F J-Strauss-Allee 11, 93042, Germany.
pubmed:publicationType
Journal Article