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Horm Metab Res 2008; 40(6): 369-374
DOI: 10.1055/s-2008-1062739
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Mitogenic Effect of the Insulin Analogue Glargine in Malignant Cells in Comparison with Insulin and IGF-I

E. Liefvendahl 1 , H. J. Arnqvist 1
  • 1Diabetes Research Centre and Division of Cell Biology, Department of Biomedicine and Surgery, Faculty of Health Sciences, Linköping University, Linköping, Sweden
Further Information

Publication History

received 04.06.2007

accepted 12.11.2007

Publication Date:
07 April 2008 (online)

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Abstract

The aim of the study was to investigate if the insulin analogue glargine, with an increased affinity for the IGF-I receptor (IGF-IR), affects the cell growth to a larger extent than human insulin in malignant cells expressing IGF-IRs. The breast cancer cell lines MCF-7 and SKBR-3, and the osteosarcoma cell line SaOS-2 were used. Gene expression was determined by real-time RT-PCR and receptor protein quantified by ELISAs. Receptor phosphorylation was assessed by immunoprecipitation and Western blot. Mitogenic effect was determined as 3H-thymidine incorporation into DNA. The gene expression of insulin receptor (IR) varied between 4.3-7.5·10-3 and the expression of IGF-IR between 7.7-147.7·10-3 in relation to GAPDH (glyceraldehyde-3-phosphate dehydrogenase). Insulin receptor and IGF-IR protein varied between 2.0-4.1 ng/mg protein and 2.0-40.4 ng/mg protein, respectively. The IGF-IR was phosphorylated by IGF-I at a concentration of 10-10-10-9 M. All three polypeptides stimulated DNA synthesis in MCF-7, SKBR-3, and SaOS-2 cells. SaOS-2 cells were more sensitive to IGF-I than to insulin and glargine. MCF-7 cells were more sensitive to des(1-3)IGF-I than to IGF-I. In SKBR-3 and SaOS-2 cells, glargine tended to be more potent than human insulin to stimulate DNA synthesis. Our results suggest that glargine, compared to human insulin, has little or no increased mitogenic effect in malignant cells expressing IGF-IRs.

Key words

cancer cell line - sarcoma cell line - receptors - tyrosine kinase - DNA synthesis

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Correspondence

H.J. Arnqvist

Department of Biomedicine and Surgery

Division of Cell Biology

Linköping University

581 85 Linköping

Sweden

Phone: +46/13/22 33 89

Fax: +46/13/22 42 73

Email: hans.arnqvist@ibk.liu.se

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