Universität zu Köln

Mori, Yusaku, Ko, Eunhyoung, Furrer, Rudolf, Qu, Linda C., Wiber, Stuart C., Fantus, I. George, Thevis, Mario, Medline, Alan and Giacca, Adria (2018). Effects of insulin and analogues on carcinogen-induced mammary tumours in high-fat-fed rats. Endocr. Connect., 7 (5). S. 739 - 749. BRISTOL: BIOSCIENTIFICA LTD. ISSN 2049-3614

Full text not available from this repository.

Abstract

It is not fully clarified whether insulin glargine, an analogue with a high affinity for insulinlike 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 (15U/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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mori, Yusaku UNSPECIFIED UNSPECIFIED UNSPECIFIED Ko, Eunhyoung UNSPECIFIED UNSPECIFIED UNSPECIFIED Furrer, Rudolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Qu, Linda C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiber, Stuart C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fantus, I. George UNSPECIFIED UNSPECIFIED UNSPECIFIED Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Medline, Alan UNSPECIFIED UNSPECIFIED UNSPECIFIED Giacca, Adria UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-187544
DOI:	10.1530/EC-17-0358
Journal or Publication Title:	Endocr. Connect.
Volume:	7
Number:	5
Page Range:	S. 739 - 749
Date:	2018
Publisher:	BIOSCIENTIFICA LTD
Place of Publication:	BRISTOL
ISSN:	2049-3614
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BREAST-CANCER; IGF-I; BASAL INSULIN; GLARGINE; GROWTH; RISK; MALIGNANCIES; METABOLISM; THERAPY; INTACT Multiple languages Endocrinology & Metabolism Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18754