Non-metabolisable insulin glargine does not promote breast cancer growth in a mouse model of type 2 diabetes.
Diabetologia
; 59(9): 2018-25, 2016 09.
Article
em En
| MEDLINE
| ID: mdl-27241182
ABSTRACT
AIMS/HYPOTHESIS:
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.METHODS:
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.RESULTS:
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. CONCLUSIONS/INTERPRETATION:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Mamárias Animais
/
Diabetes Mellitus Tipo 2
/
Insulina Glargina
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Diabetologia
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos