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Effects of insulin and analogues on carcinogen-induced mammary tumours in high-fat-fed rats
It is not fully clarified whether insulin glargine, an analogue with a high affinity for insulin-like growth factor-1 receptor (IGF-1R), increases the risk for cancers that abundantly express IGF-1R such as breast cancer or some types of breast cancer. To gain insight into this issue, female Sprague...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Bioscientifica Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958747/ https://www.ncbi.nlm.nih.gov/pubmed/29692348 http://dx.doi.org/10.1530/EC-17-0358 |
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author | Mori, Yusaku Ko, Eunhyoung Furrer, Rudolf Qu, Linda C Wiber, Stuart C Fantus, I George Thevis, Mario Medline, Alan Giacca, Adria |
author_facet | Mori, Yusaku Ko, Eunhyoung Furrer, Rudolf Qu, Linda C Wiber, Stuart C Fantus, I George Thevis, Mario Medline, Alan Giacca, Adria |
author_sort | Mori, Yusaku |
collection | PubMed |
description | It is not fully clarified whether insulin glargine, an analogue with a high affinity for insulin-like growth factor-1 receptor (IGF-1R), increases the risk for cancers that abundantly express IGF-1R such as breast cancer or some types of breast cancer. To gain insight into this issue, female Sprague–Dawley rats fed a high-fat diet were given the carcinogen N-methyl-N-nitrosourea and randomly assigned to vehicle (control), NPH (unmodified human insulin), glargine or detemir (n = 30 per treatment). Insulins were given subcutaneously (15 U/kg/day) 5 days a week. Mammary tumours were counted twice weekly, and after 6 weeks of treatment, extracted for analysis. None of the insulin-treated groups had increased mammary tumour incidence at any time compared with control. At 6 weeks, tumour multiplicity was increased with NPH or glargine (P < 0.05) and tended to be increased with detemir (P = 0.2); however, there was no difference among insulins (number of tumours per rat: control = 0.8 ± 0.1, NPH = 1.8 ± 0.3, glargine = 1.5 ± 0.4, detemir = 1.4 ± 0.4; number of tumours per tumour-bearing rat: control = 1.3 ± 0.1, NPH = 2.2 ± 0.4, glargine = 2.7 ± 0.5, detemir = 2.3 ± 0.5). IGF-1R expression in tumours was lower than that in Michigan Cancer Foundation-7 (MCF-7) cells, a cell line that shows greater proliferation with glargine than unmodified insulin. In rats, glargine was rapidly metabolised to M1 that does not have greater affinity for IGF-1R. In conclusion, in this model of oestrogen-dependent breast cancer in insulin-resistant rats, insulin and insulin analogues increased tumour multiplicity with no difference between insulin types. |
format | Online Article Text |
id | pubmed-5958747 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Bioscientifica Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-59587472018-05-24 Effects of insulin and analogues on carcinogen-induced mammary tumours in high-fat-fed rats Mori, Yusaku Ko, Eunhyoung Furrer, Rudolf Qu, Linda C Wiber, Stuart C Fantus, I George Thevis, Mario Medline, Alan Giacca, Adria Endocr Connect Research It is not fully clarified whether insulin glargine, an analogue with a high affinity for insulin-like growth factor-1 receptor (IGF-1R), increases the risk for cancers that abundantly express IGF-1R such as breast cancer or some types of breast cancer. To gain insight into this issue, female Sprague–Dawley rats fed a high-fat diet were given the carcinogen N-methyl-N-nitrosourea and randomly assigned to vehicle (control), NPH (unmodified human insulin), glargine or detemir (n = 30 per treatment). Insulins were given subcutaneously (15 U/kg/day) 5 days a week. Mammary tumours were counted twice weekly, and after 6 weeks of treatment, extracted for analysis. None of the insulin-treated groups had increased mammary tumour incidence at any time compared with control. At 6 weeks, tumour multiplicity was increased with NPH or glargine (P < 0.05) and tended to be increased with detemir (P = 0.2); however, there was no difference among insulins (number of tumours per rat: control = 0.8 ± 0.1, NPH = 1.8 ± 0.3, glargine = 1.5 ± 0.4, detemir = 1.4 ± 0.4; number of tumours per tumour-bearing rat: control = 1.3 ± 0.1, NPH = 2.2 ± 0.4, glargine = 2.7 ± 0.5, detemir = 2.3 ± 0.5). IGF-1R expression in tumours was lower than that in Michigan Cancer Foundation-7 (MCF-7) cells, a cell line that shows greater proliferation with glargine than unmodified insulin. In rats, glargine was rapidly metabolised to M1 that does not have greater affinity for IGF-1R. In conclusion, in this model of oestrogen-dependent breast cancer in insulin-resistant rats, insulin and insulin analogues increased tumour multiplicity with no difference between insulin types. Bioscientifica Ltd 2018-04-24 /pmc/articles/PMC5958747/ /pubmed/29692348 http://dx.doi.org/10.1530/EC-17-0358 Text en © 2018 The authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Research Mori, Yusaku Ko, Eunhyoung Furrer, Rudolf Qu, Linda C Wiber, Stuart C Fantus, I George Thevis, Mario Medline, Alan Giacca, Adria Effects of insulin and analogues on carcinogen-induced mammary tumours in high-fat-fed rats |
title | Effects of insulin and analogues on carcinogen-induced mammary tumours in high-fat-fed rats |
title_full | Effects of insulin and analogues on carcinogen-induced mammary tumours in high-fat-fed rats |
title_fullStr | Effects of insulin and analogues on carcinogen-induced mammary tumours in high-fat-fed rats |
title_full_unstemmed | Effects of insulin and analogues on carcinogen-induced mammary tumours in high-fat-fed rats |
title_short | Effects of insulin and analogues on carcinogen-induced mammary tumours in high-fat-fed rats |
title_sort | effects of insulin and analogues on carcinogen-induced mammary tumours in high-fat-fed rats |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958747/ https://www.ncbi.nlm.nih.gov/pubmed/29692348 http://dx.doi.org/10.1530/EC-17-0358 |
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