title: Non-metabolisable insulin glargine does not promote breast cancer growth in a mouse model of type 2 diabetes.
abstract: Previous epidemiological studies have reported a potential link between insulin analogues and breast cancer; however, a prospective randomised controlled trial showed neutral effects of insulin glargine on cancer risk. Insulin glargine is metabolised in vivo to an M1 metabolite. A question remains whether a subset of individuals with slower rates of glargine metabolism or who are on high doses could, theoretically, have an increased risk of cancer progression if a tumour is already present. In this study, we aimed to determine whether a non-metabolisable form of insulin glargine induced murine breast cancer growth.
  
  
  
  A mouse model of type 2 diabetes (MKR) was used for these studies. MKR mice were injected with two murine mammary cancer cell lines: Mvt-1 cells (derived from MMTV-c-Myc/Vegf tumours) and Met1 cells (derived from MMTV-polyoma virus middle T antigen tumours). Mice were treated with 25 U/kg per day of the long-acting insulin analogues, insulin glargine, insulin detemir, insulin degludec or non-metabolisable glargine, or vehicle.
  
  
  
  No difference in tumour growth was seen in terms of tumour size after insulin glargine, detemir, degludec or vehicle injections. Non-metabolisable glargine did not increase tumour growth compared with insulin glargine or vehicle. Insulin glargine and non-metabolisable glargine led to insulin receptor phosphorylation in vivo rather than IGF-1 receptor phosphorylation.
  
  
  
  These results demonstrate that in a mouse model of type 2 diabetes, at high concentrations, basal insulin analogues and a non-metabolisable glargine analogue do not promote the progression of breast tumours.
authors.affiliation: Division of Endocrinology, Diabetes and Bone Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1055, New York, NY, 10029, USA. emily.gallagher@mssm.edu.
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Gallagher
authors.affiliation: Division of Endocrinology, Diabetes and Bone Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1055, New York, NY, 10029, USA.
authors.forename: Zara
authors.initials: Z
authors.lastname: Zelenko
authors.affiliation: Division of Endocrinology, Diabetes and Bone Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1055, New York, NY, 10029, USA.
authors.forename: Aviva
authors.initials: A
authors.lastname: Tobin-Hess
authors.affiliation: Diabetes Research & Translational Medicine, Insulin Biology, Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Werner
authors.affiliation: Diabetes Research & Translational Medicine, Insulin Biology, Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Tennagels
authors.affiliation: Division of Endocrinology, Diabetes and Bone Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1055, New York, NY, 10029, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: LeRoith
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D007328:Insulin / Q000737:chemistry / Q000627:therapeutic use; D000069036:Insulin Glargine / Q000009:adverse effects* / Q000737:chemistry / Q000627:therapeutic use; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced* / Q000473:pathology*; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D011972:Receptor, Insulin / Q000378:metabolism; D017451:Receptors, Somatomedin / Q000378:metabolism
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D017451:Receptors, Somatomedin; D000069036:Insulin Glargine; D011972:Receptor, Insulin
keywords: Breast cancer; Insulin analogues; Insulin receptor; Insulin-like growth factor receptor; Type 2 diabetes