Insulin-sensitizing therapy attenuates type 2 diabetes-mediated mammary tumor progression

Yvonne Fierz, Ruslan Novosyadlyy, Archana Vijayakumar, Shoshana Yakar, Derek LeRoith

Research output: Contribution to journalArticle

Abstract

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 β3-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.

Original languageEnglish (US)
Pages (from-to)686-693
Number of pages8
JournalDiabetes
Volume59
Issue number3
DOIs
StatePublished - Mar 2010

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Type 2 Diabetes Mellitus
Insulin
Breast Neoplasms
Therapeutics
Breast
Polyomavirus
Adrenergic Agonists
IGF Type 1 Receptor
Mortality
Hyperinsulinism
Human Mammary Glands
Tumor Cell Line
Oncogenes
Neoplasms
Research Design
Epithelium
Phosphorylation
Pharmacology

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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Insulin-sensitizing therapy attenuates type 2 diabetes-mediated mammary tumor progression. / Fierz, Yvonne; Novosyadlyy, Ruslan; Vijayakumar, Archana; Yakar, Shoshana; LeRoith, Derek.

In: Diabetes, Vol. 59, No. 3, 03.2010, p. 686-693.

Research output: Contribution to journalArticle

Fierz, Y, Novosyadlyy, R, Vijayakumar, A, Yakar, S & LeRoith, D 2010, 'Insulin-sensitizing therapy attenuates type 2 diabetes-mediated mammary tumor progression', Diabetes, vol. 59, no. 3, pp. 686-693. https://doi.org/10.2337/db09-1291
Fierz, Yvonne ; Novosyadlyy, Ruslan ; Vijayakumar, Archana ; Yakar, Shoshana ; LeRoith, Derek. / Insulin-sensitizing therapy attenuates type 2 diabetes-mediated mammary tumor progression. In: Diabetes. 2010 ; Vol. 59, No. 3. pp. 686-693.
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