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

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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:
CreatorsEmailORCIDORCID Put Code
Mori, YusakuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ko, EunhyoungUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Furrer, RudolfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Qu, Linda C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiber, Stuart C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fantus, I. GeorgeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thevis, MarioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Medline, AlanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Giacca, AdriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
BREAST-CANCER; IGF-I; BASAL INSULIN; GLARGINE; GROWTH; RISK; MALIGNANCIES; METABOLISM; THERAPY; INTACTMultiple languages
Endocrinology & MetabolismMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/18754

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