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Mitogenic effect of the insulin analogue glargine in malignant cells in comparison with insulin and IGF-I
Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
2008 (English)In: Hormone and Metabolic Research, ISSN 0018-5043, Vol. 40, no 6, 369-374 p.Article in journal (Refereed) Published
Abstract [en]

The aim of the study was to investigate if the insulin analogue glargine, with an increased affinity for the IGF-I receptor (ICF-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 immuno-precipitation 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 -10-10-10M. 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(l-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. © Georg Thieme Verlag KG Stuttgart · New York.

Place, publisher, year, edition, pages
2008. Vol. 40, no 6, 369-374 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-43387DOI: 10.1055/s-2008-1062739Local ID: 73689OAI: oai:DiVA.org:liu-43387DiVA: diva2:264246
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2011-01-10

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Liefvendahl, EllinorArnqvist, Hans

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