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Could recombinant insulin compounds contribute to adenocarcinoma progression by stimulating local angiogenesis?
AIMS/HYPOTHESIS: Negative effects on the progression of adenocarcinomas by hyperinsulinaemia and the insulin analogue glargine (A21Gly,B31Arg,B32Arg human insulin) have recently been suggested. Most actions of this insulin analogue have hitherto been explained by direct stimulation of growth potenti...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Springer-Verlag
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2850513/ https://www.ncbi.nlm.nih.gov/pubmed/20182859 http://dx.doi.org/10.1007/s00125-010-1687-y |
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author | Rensing, K. L. Houttuijn Bloemendaal, F. M. Weijers, E. M. Richel, D. J. Büller, H. R. Koolwijk, P. van der Loos, C. M. Twickler, Th. B. von der Thüsen, J. H. |
author_facet | Rensing, K. L. Houttuijn Bloemendaal, F. M. Weijers, E. M. Richel, D. J. Büller, H. R. Koolwijk, P. van der Loos, C. M. Twickler, Th. B. von der Thüsen, J. H. |
author_sort | Rensing, K. L. |
collection | PubMed |
description | AIMS/HYPOTHESIS: Negative effects on the progression of adenocarcinomas by hyperinsulinaemia and the insulin analogue glargine (A21Gly,B31Arg,B32Arg human insulin) have recently been suggested. Most actions of this insulin analogue have hitherto been explained by direct stimulation of growth potential of neoplastic cells and by its IGF-1 related properties. However, insulin-stimulated angiogenesis could be an additional factor involved in tumour progression and clinical outcomes associated with cancer. METHODS: Five types of human adenocarcinoma (breast, colon, pancreas, lung and kidney) were evaluated for the presence of insulin receptors (IRs) on angiogenic structures. In an in vitro angiogenesis assay, various commercially available insulin compounds were evaluated for their potential to increase capillary-like tube formation of human microvascular endothelial cells (hMVEC). Insulin compounds used were: human insulin, insulin lispro (B28Lys,B29Pro human insulin), insulin glargine and insulin detemir (B29Lys[e-tetradecanoyl],desB30 human insulin). RESULTS: Insulin receptors were found to be strongly expressed on the endothelium of microvessels in all evaluated adenocarcinomas, in addition to variable expression on tumour cells. Low or no detectable expression of IRs was seen on microvessels in extratumoral stroma. Incubation with commercially available insulin compounds increased capillary-like tube formation of hMVEC in vitro. CONCLUSIONS/INTERPRETATION: Our results suggest that all tested insulin compounds may stimulate tumour growth by enhancing local angiogenesis. Future studies need to confirm the association between insulin therapy in type 2 diabetes and tumour progression. |
format | Text |
id | pubmed-2850513 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Springer-Verlag |
record_format | MEDLINE/PubMed |
spelling | pubmed-28505132010-04-16 Could recombinant insulin compounds contribute to adenocarcinoma progression by stimulating local angiogenesis? Rensing, K. L. Houttuijn Bloemendaal, F. M. Weijers, E. M. Richel, D. J. Büller, H. R. Koolwijk, P. van der Loos, C. M. Twickler, Th. B. von der Thüsen, J. H. Diabetologia Short Communication AIMS/HYPOTHESIS: Negative effects on the progression of adenocarcinomas by hyperinsulinaemia and the insulin analogue glargine (A21Gly,B31Arg,B32Arg human insulin) have recently been suggested. Most actions of this insulin analogue have hitherto been explained by direct stimulation of growth potential of neoplastic cells and by its IGF-1 related properties. However, insulin-stimulated angiogenesis could be an additional factor involved in tumour progression and clinical outcomes associated with cancer. METHODS: Five types of human adenocarcinoma (breast, colon, pancreas, lung and kidney) were evaluated for the presence of insulin receptors (IRs) on angiogenic structures. In an in vitro angiogenesis assay, various commercially available insulin compounds were evaluated for their potential to increase capillary-like tube formation of human microvascular endothelial cells (hMVEC). Insulin compounds used were: human insulin, insulin lispro (B28Lys,B29Pro human insulin), insulin glargine and insulin detemir (B29Lys[e-tetradecanoyl],desB30 human insulin). RESULTS: Insulin receptors were found to be strongly expressed on the endothelium of microvessels in all evaluated adenocarcinomas, in addition to variable expression on tumour cells. Low or no detectable expression of IRs was seen on microvessels in extratumoral stroma. Incubation with commercially available insulin compounds increased capillary-like tube formation of hMVEC in vitro. CONCLUSIONS/INTERPRETATION: Our results suggest that all tested insulin compounds may stimulate tumour growth by enhancing local angiogenesis. Future studies need to confirm the association between insulin therapy in type 2 diabetes and tumour progression. Springer-Verlag 2010-02-25 2010 /pmc/articles/PMC2850513/ /pubmed/20182859 http://dx.doi.org/10.1007/s00125-010-1687-y Text en © The Author(s) 2010 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. |
spellingShingle | Short Communication Rensing, K. L. Houttuijn Bloemendaal, F. M. Weijers, E. M. Richel, D. J. Büller, H. R. Koolwijk, P. van der Loos, C. M. Twickler, Th. B. von der Thüsen, J. H. Could recombinant insulin compounds contribute to adenocarcinoma progression by stimulating local angiogenesis? |
title | Could recombinant insulin compounds contribute to adenocarcinoma progression by stimulating local angiogenesis? |
title_full | Could recombinant insulin compounds contribute to adenocarcinoma progression by stimulating local angiogenesis? |
title_fullStr | Could recombinant insulin compounds contribute to adenocarcinoma progression by stimulating local angiogenesis? |
title_full_unstemmed | Could recombinant insulin compounds contribute to adenocarcinoma progression by stimulating local angiogenesis? |
title_short | Could recombinant insulin compounds contribute to adenocarcinoma progression by stimulating local angiogenesis? |
title_sort | could recombinant insulin compounds contribute to adenocarcinoma progression by stimulating local angiogenesis? |
topic | Short Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2850513/ https://www.ncbi.nlm.nih.gov/pubmed/20182859 http://dx.doi.org/10.1007/s00125-010-1687-y |
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