liu.seSearch for publications in DiVA
Change search
Link to record
Permanent link

Direct link
BETA
Liefvendahl, Ellinor
Publications (2 of 2) Show all publications
Chisalita, I. S., Johansson, G., Liefvendahl, E., Bäck, K. & Arnqvist, H. (2009). Human aortic smooth muscle cells are insulin resistant at the receptor level but sensitive to IGF1 and IGF2. Journal of Molecular Endocrinology, 43(5-6), 231-239
Open this publication in new window or tab >>Human aortic smooth muscle cells are insulin resistant at the receptor level but sensitive to IGF1 and IGF2
Show others...
2009 (English)In: Journal of Molecular Endocrinology, ISSN 0952-5041, E-ISSN 1479-6813, Vol. 43, no 5-6, p. 231-239Article in journal (Refereed) Published
Abstract [en]

Whether insulin, in physiological concentrations, has direct effects on vascular smooth muscle cells (VSMC) remains controversial. Our aim was to characterize the mechanism for insulin resistance in VSMCs. For comparison, effects of insulin-like growth factor (IGF)-I and IGF-II were also studied. Cultured human aortic smooth muscle cells (HASMC) were used. Receptor mRNA was analysed by quantitative RT-PCR and receptor protein by ELISA and Western Blot. The biological effects were studied by thymidine incorporation and glucose accumulation.

In HASMC both mRNA and protein expression of IGF-I receptors (IGF-IR) were 5 fold higher compared to insulin receptor (IR). IR isoform A mRNA was 13 times more expressed than IR isoform B. Immunoprecipitation and Western blot showed co precipitation of IR and IGF-IR indicating the presence of hybrid IR/IGF-IR.

Phosphorylation of the IGF-IR β-subunit was obtained by IGF-I 10-9-10-8mol l-1 and IGF-II 10-8mol l-1. IR β-subunit was phosphorylated by IGF-I 10-8mol l-1 but not by insulin. IGF-I stimulated IRS-I at 10-8mol l-1, Akt and Erk 1/2 at 10-9-10-8mol l-1, respectively. IGF-II stimulated Akt at 10-8mol l-1 whereas insulin had no effect. IGF-I and IGF-II at a concentration of 10-8-10-7mol l-1 significantly stimulated 3H-thymidine incorporation, whereas insulin did not. 14C-Glucose accumulation was stimulated by IGF-I or IGF-II 10-8-10-7mol l-1, and also by insulin 10-7mol l-1.

Our results suggest that IGF-IR and hybrid IR/IGF-IR are activated by physiological concentrations of IGF-I and IGF-II in HASMC and this causes downstream signaling and biological effects, while insulin has no effect on its receptor or downstream signaling probably due to a preponderance of IGF-IR and incorporation of IR into hybrid IR/IGF-IR.

Keywords
Receptors, insulin, IGF-I, IGF-II, IRS-1, Erk 1/2, Akt, DNA-synthesis, glucose accumulation.
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-19283 (URN)10.1677/JME-09-0021 (DOI)
Available from: 2009-06-16 Created: 2009-06-16 Last updated: 2017-12-13Bibliographically approved
Liefvendahl, E. & Arnqvist, H. (2008). Mitogenic effect of the insulin analogue glargine in malignant cells in comparison with insulin and IGF-I. Hormone and Metabolic Research, 40(6), 369-374
Open this publication in new window or tab >>Mitogenic effect of the insulin analogue glargine in malignant cells in comparison with insulin and IGF-I
2008 (English)In: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 40, no 6, p. 369-374Article 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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-43387 (URN)10.1055/s-2008-1062739 (DOI)73689 (Local ID)73689 (Archive number)73689 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
Organisations

Search in DiVA

Show all publications