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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
|
| pubmed:dateCreated |
1998-4-14
|
| pubmed:abstractText |
It is not clear which growth factors are crucial for the survival, proliferation, and differentiation of pancreatic beta-cells. We used the relatively differentiated rat insulinoma cell line INS-1 to elucidate this issue. Responsiveness of the DNA synthesis of serum-starved cells was studied to a wide variety of growth factors. The most potent stimulators were PRL, GH, and betacellulin, a member of the epidermal growth factor (EGF) family that has not previously been shown to be mitogenic for beta-cells. In addition to these, only vascular endothelial growth factor, insulin-like growth factor-1 and -2, had significant mitogenic activity, whereas hepatocyte growth factor, nerve growth factor-beta, platelet-derived growth factors, basic fibroblast growth factor, EGF, transforming growth factor-alpha (TGF-alpha), neu differentiation factor, and TGF-beta were inactive. None of these factors affected the insulin content of INS-1 cells. In contrast, certain differentiation factors, including nicotinamide, sodium butyrate, activin A, and 1,25-dihydroxyvitamin D3 inhibited the DNA synthesis and increased the insulin content. Also all-trans-retinoic acid had an inhibitory effect on cell DNA synthesis but no effect on insulin content. From these findings betacellulin emerges as a novel growth factor for the beta-cell. Half-maximal stimulation of INS-1 DNA synthesis was obtained with 25 pM betacellulin. Interestingly, betacellulin had no effect on RINm5F cells, whereas both EGF and TGF-alpha were slightly mitogenic. These effects may possibly be explained by differential expression of the erbB receptor tyrosine kinases. In RINm5F cells a spectrum of erbB gene expression was detected (EGF receptor/erbB-1, erbB-2/neu, and erbB-3), whereas INS-1 cells showed only expression of EGF receptor. Expression of the erbB-4 gene was undetectable in these cell lines. In summary, our results suggest that the INS-1 cell line is a suitable model for the study of beta-cell growth and differentiation because the responses to previously identified beta-cell mitogens were essentially similar to those reported in primary cells. In addition, we have identified betacellulin as a possible modulator of beta-cell growth.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Human Growth Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor II,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogens,
http://linkedlifedata.com/resource/pubmed/chemical/Prolactin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/betacellulin
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
0013-7227
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
139
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1494-9
|
| pubmed:dateRevised |
2011-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:9528926-Animals,
pubmed-meshheading:9528926-Cell Differentiation,
pubmed-meshheading:9528926-Cell Division,
pubmed-meshheading:9528926-Cell Line,
pubmed-meshheading:9528926-DNA,
pubmed-meshheading:9528926-Gene Expression,
pubmed-meshheading:9528926-Growth Substances,
pubmed-meshheading:9528926-Human Growth Hormone,
pubmed-meshheading:9528926-Humans,
pubmed-meshheading:9528926-Insulin,
pubmed-meshheading:9528926-Insulin-Like Growth Factor I,
pubmed-meshheading:9528926-Insulin-Like Growth Factor II,
pubmed-meshheading:9528926-Insulinoma,
pubmed-meshheading:9528926-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:9528926-Islets of Langerhans,
pubmed-meshheading:9528926-Mitogens,
pubmed-meshheading:9528926-Pancreatic Neoplasms,
pubmed-meshheading:9528926-Prolactin,
pubmed-meshheading:9528926-Rats,
pubmed-meshheading:9528926-Receptor, Epidermal Growth Factor,
pubmed-meshheading:9528926-Recombinant Proteins
|
| pubmed:year |
1998
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| pubmed:articleTitle |
Growth factor-mediated proliferation and differentiation of insulin-producing INS-1 and RINm5F cells: identification of betacellulin as a novel beta-cell mitogen.
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| pubmed:affiliation |
Transplantation Laboratory, Haartman Institute and Children's Hospital, University of Helsinki, Finland. mari.huotari@helsinki.fi
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|