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

Author:

Mori Yusaku12,Ko Eunhyoung1,Furrer Rudolf3,Qu Linda C1,Wiber Stuart C1,Fantus I George456,Thevis Mario7,Medline Alan89,Giacca Adria10

Affiliation:

1. 1Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

2. 2Department of Diabetes, Metabolism, and Endocrinology, Showa University School of Medicine, Shinagawa, Tokyo, Japan

3. 3Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

4. 4Departments of Medicine and Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

5. 5Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada

6. 6Division of Endocrinology and Metabolism, Leadership Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada

7. 7Center for Preventive Doping Research and Institute of Biochemistry, German Sport University Cologne, Cologne, Germany

8. 8Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada

9. 9Department of Pathology, Humber River Regional Hospital, Toronto, Ontario, Canada

10. 10Departments of Physiology and Medicine, Institute of Medical Science, Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada

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.

Publisher

Bioscientifica

Subject

Endocrinology,Endocrinology, Diabetes and Metabolism,Internal Medicine

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3