Cargando…

Insulin-Sensitizing Therapy Attenuates Type 2 Diabetes–Mediated Mammary Tumor Progression

OBJECTIVE: Type 2 diabetes increases breast cancer risk and mortality, and hyperinsulinemia has been identified as a major factor linking these two diseases. Thus, we hypothesized that pharmacological reduction of elevated insulin levels would attenuate type 2 diabetes–mediated mammary tumor progres...

Descripción completa

Detalles Bibliográficos
Autores principales: Fierz, Yvonne, Novosyadlyy, Ruslan, Vijayakumar, Archana, Yakar, Shoshana, LeRoith, Derek
Formato: Texto
Lenguaje:English
Publicado: American Diabetes Association 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828655/
https://www.ncbi.nlm.nih.gov/pubmed/19959755
http://dx.doi.org/10.2337/db09-1291
_version_ 1782178030309867520
author Fierz, Yvonne
Novosyadlyy, Ruslan
Vijayakumar, Archana
Yakar, Shoshana
LeRoith, Derek
author_facet Fierz, Yvonne
Novosyadlyy, Ruslan
Vijayakumar, Archana
Yakar, Shoshana
LeRoith, Derek
author_sort Fierz, Yvonne
collection PubMed
description OBJECTIVE: Type 2 diabetes increases breast cancer risk and mortality, and hyperinsulinemia has been identified as a major factor linking these two diseases. Thus, we hypothesized that pharmacological reduction of elevated insulin levels would attenuate type 2 diabetes–mediated mammary tumor progression. RESEARCH DESIGN AND METHODS: We studied mammary tumor development in MKR(+/+) mice, a nonobese, hyperinsulinemic mouse model of type 2 diabetes. MKR(+/+) mice were either crossed with mice expressing the polyoma virus middle T oncogene specifically in the mammary gland or inoculated orthotopically with the mouse mammary tumor cell lines Met-1 and MCNeuA. MKR(+/+) or control mice harboring tumors were treated with CL-316243, a specific β(3)-adrenergic receptor agonist, which sensitizes insulin action but has no direct effect on the mouse mammary epithelium or Met-1 and MCNeuA cells. RESULTS: CL-316243 treatment significantly reduced the elevated insulin levels in MKR(+/+) mice and, as a consequence, attenuated mammary tumor progression in the three tumor models tested. This effect was accompanied by reductions in phosphorylation of insulin and IGF-I receptors in transformed mammary tissue. CONCLUSIONS: Insulin-sensitizing treatment is sufficient to abrogate type 2 diabetes–mediated mammary tumor progression. Therefore, early administration of insulin-sensitizing therapy may reduce breast cancer risk and mortality in patients with type 2 diabetes.
format Text
id pubmed-2828655
institution National Center for Biotechnology Information
language English
publishDate 2010
publisher American Diabetes Association
record_format MEDLINE/PubMed
spelling pubmed-28286552011-03-01 Insulin-Sensitizing Therapy Attenuates Type 2 Diabetes–Mediated Mammary Tumor Progression Fierz, Yvonne Novosyadlyy, Ruslan Vijayakumar, Archana Yakar, Shoshana LeRoith, Derek Diabetes Original Article OBJECTIVE: Type 2 diabetes increases breast cancer risk and mortality, and hyperinsulinemia has been identified as a major factor linking these two diseases. Thus, we hypothesized that pharmacological reduction of elevated insulin levels would attenuate type 2 diabetes–mediated mammary tumor progression. RESEARCH DESIGN AND METHODS: We studied mammary tumor development in MKR(+/+) mice, a nonobese, hyperinsulinemic mouse model of type 2 diabetes. MKR(+/+) mice were either crossed with mice expressing the polyoma virus middle T oncogene specifically in the mammary gland or inoculated orthotopically with the mouse mammary tumor cell lines Met-1 and MCNeuA. MKR(+/+) or control mice harboring tumors were treated with CL-316243, a specific β(3)-adrenergic receptor agonist, which sensitizes insulin action but has no direct effect on the mouse mammary epithelium or Met-1 and MCNeuA cells. RESULTS: CL-316243 treatment significantly reduced the elevated insulin levels in MKR(+/+) mice and, as a consequence, attenuated mammary tumor progression in the three tumor models tested. This effect was accompanied by reductions in phosphorylation of insulin and IGF-I receptors in transformed mammary tissue. CONCLUSIONS: Insulin-sensitizing treatment is sufficient to abrogate type 2 diabetes–mediated mammary tumor progression. Therefore, early administration of insulin-sensitizing therapy may reduce breast cancer risk and mortality in patients with type 2 diabetes. American Diabetes Association 2010-03 2009-12-03 /pmc/articles/PMC2828655/ /pubmed/19959755 http://dx.doi.org/10.2337/db09-1291 Text en © 2010 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Article
Fierz, Yvonne
Novosyadlyy, Ruslan
Vijayakumar, Archana
Yakar, Shoshana
LeRoith, Derek
Insulin-Sensitizing Therapy Attenuates Type 2 Diabetes–Mediated Mammary Tumor Progression
title Insulin-Sensitizing Therapy Attenuates Type 2 Diabetes–Mediated Mammary Tumor Progression
title_full Insulin-Sensitizing Therapy Attenuates Type 2 Diabetes–Mediated Mammary Tumor Progression
title_fullStr Insulin-Sensitizing Therapy Attenuates Type 2 Diabetes–Mediated Mammary Tumor Progression
title_full_unstemmed Insulin-Sensitizing Therapy Attenuates Type 2 Diabetes–Mediated Mammary Tumor Progression
title_short Insulin-Sensitizing Therapy Attenuates Type 2 Diabetes–Mediated Mammary Tumor Progression
title_sort insulin-sensitizing therapy attenuates type 2 diabetes–mediated mammary tumor progression
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828655/
https://www.ncbi.nlm.nih.gov/pubmed/19959755
http://dx.doi.org/10.2337/db09-1291
work_keys_str_mv AT fierzyvonne insulinsensitizingtherapyattenuatestype2diabetesmediatedmammarytumorprogression
AT novosyadlyyruslan insulinsensitizingtherapyattenuatestype2diabetesmediatedmammarytumorprogression
AT vijayakumararchana insulinsensitizingtherapyattenuatestype2diabetesmediatedmammarytumorprogression
AT yakarshoshana insulinsensitizingtherapyattenuatestype2diabetesmediatedmammarytumorprogression
AT leroithderek insulinsensitizingtherapyattenuatestype2diabetesmediatedmammarytumorprogression