Effects of insulin and analogues on carcinogen-induced mammary tumours in high-fat-fed rats. Issue 5 (May 2018)

• Record Type: Journal Article
• Authors: Mori, Yusaku; Ko, Eunhyoung; Furrer, Rudolf; Qu, Linda C; Wiber, Stuart C; Fantus, I George; Thevis, Mario; Medline, Alan; Giacca, Adria
• Is Part Of: Endocrine connections. Volume 7:Issue 5(2018)
• Page Start: 739
• Page End: 748
• Publication Date: 2018-05
• Subjects: detemir -- glargine -- insulin -- mammary tumour -- rat; Endocrinology -- Periodicals; 616.4005
• DOI: 10.1530/EC-17-0358
• Languages: English
• ISSNs: 2049-3614

Abstract

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.