Effects of insulin and analogues on carcinogen-induced mammary tumours in high-fat-fed rats

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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.

in: Endocrine connections, Jahrgang 7, Nr. 5, 05.2018, S. 739-748.

Publikationen: Beitrag in FachzeitschriftZeitschriftenaufsätzeForschungBegutachtung

Harvard

Mori, Y, Ko, E, Furrer, R, Qu, LC, Wiber, SC, Fantus, IG, Thevis, M, Medline, A & Giacca, A 2018, 'Effects of insulin and analogues on carcinogen-induced mammary tumours in high-fat-fed rats', Endocrine connections, Jg. 7, Nr. 5, S. 739-748. https://doi.org/10.1530/EC-17-0358

APA

Mori, Y., Ko, E., Furrer, R., Qu, L. C., Wiber, S. C., Fantus, I. G., Thevis, M., Medline, A., & Giacca, A. (2018). Effects of insulin and analogues on carcinogen-induced mammary tumours in high-fat-fed rats. Endocrine connections, 7(5), 739-748. https://doi.org/10.1530/EC-17-0358

Vancouver

Bibtex

@article{7d6c10d138924ad28722c966cdb31429,
title = "Effects of insulin and analogues on carcinogen-induced mammary tumours in high-fat-fed rats",
abstract = "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.",
keywords = "Journal Article",
author = "Yusaku Mori and Eunhyoung Ko and Rudolf Furrer and Qu, {Linda C} and Wiber, {Stuart C} and Fantus, {I George} and Mario Thevis and Alan Medline and Adria Giacca",
note = "{\textcopyright} 2018 The authors.",
year = "2018",
month = may,
doi = "10.1530/EC-17-0358",
language = "English",
volume = "7",
pages = "739--748",
journal = "Endocrine connections",
issn = "2049-3614",
publisher = "BioScientifica Ltd.",
number = "5",

}

RIS

TY - JOUR

T1 - Effects of insulin and analogues on carcinogen-induced mammary tumours in high-fat-fed rats

AU - Mori, Yusaku

AU - Ko, Eunhyoung

AU - Furrer, Rudolf

AU - Qu, Linda C

AU - Wiber, Stuart C

AU - Fantus, I George

AU - Thevis, Mario

AU - Medline, Alan

AU - Giacca, Adria

N1 - © 2018 The authors.

PY - 2018/5

Y1 - 2018/5

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1530/EC-17-0358

DO - 10.1530/EC-17-0358

M3 - Journal articles

C2 - 29692348

VL - 7

SP - 739

EP - 748

JO - Endocrine connections

JF - Endocrine connections

SN - 2049-3614

IS - 5

ER -

ID: 3562848