Effects of insulin and analogues on carcinogen-induced mammary tumours in high-fat-fed rats.
| Autor: | Mori Y; Department of PhysiologyFaculty of Medicine, University of Toronto, Toronto, Ontario, Canada.; Department of DiabetesMetabolism, and Endocrinology, Showa University School of Medicine, Shinagawa, Tokyo, Japan., Ko E; Department of PhysiologyFaculty of Medicine, University of Toronto, Toronto, Ontario, Canada., Furrer R; Department of Nutritional SciencesFaculty of Medicine, University of Toronto, Toronto, Ontario, Canada., Qu LC; Department of PhysiologyFaculty of Medicine, University of Toronto, Toronto, Ontario, Canada., Wiber SC; Department of PhysiologyFaculty of Medicine, University of Toronto, Toronto, Ontario, Canada., Fantus IG; Departments of Medicine and PhysiologyFaculty of Medicine, University of Toronto, Toronto, Ontario, Canada.; Toronto General Research InstituteUniversity Health Network, Toronto, Ontario, Canada.; Division of Endocrinology and MetabolismLeadership Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada., Thevis M; Center for Preventive Doping Research and Institute of BiochemistryGerman Sport University Cologne, Cologne, Germany., Medline A; Department of Laboratory Medicine & PathobiologyUniversity of Toronto, Toronto, Ontario, Canada.; Department of PathologyHumber River Regional Hospital, Toronto, Ontario, Canada., Giacca A; Departments of Physiology and MedicineInstitute of Medical Science, Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada adria.giacca@utoronto.ca. |
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| Jazyk: | angličtina |
| Zdroj: | Endocrine connections [Endocr Connect] 2018 May; Vol. 7 (5), pp. 739-748. Date of Electronic Publication: 2018 Apr 24. |
| DOI: | 10.1530/EC-17-0358 |
| Abstrakt: | 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. (© 2018 The authors.) |
| Databáze: | MEDLINE |
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