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Replies to #97430 on Biotech Values

biomaven0

06/18/10 5:41 PM

#97441 RE: genisi #97430

This Lantus risk might be a legitimate issue. The concern is binding to IGF-I receptors - the Novo-Nordisk product (Levimir) was explicitly designed to bind to this receptor less than human insulin does.

Here is an old Novo PR on the subject from when this issue first arose:

http://siliconinvestor.advfn.com/readmsg.aspx?msgid=25746291

At the time I also posted this abstract:

1: Endocr Relat Cancer. 2009 Jun;16(2):429-441. Epub 2009 Jan 19.Click here to read Links
Analysis of signaling pathways related to cell proliferation stimulated by insulin analogs in human mammary epithelial cell lines.
Shukla A, Grisouard J, Ehemann V, Hermani A, Enzmann H, Mayer D.

Hormones and Signal Transduction Group, German Cancer Research Center, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 220/221, 69120 Heidelberg, Germany Federal Institute for Drugs and Medical Devices, Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Germany.

Insulin and insulin analogs stimulate proliferation of human mammary epithelial cells. We identified and analyzed the signaling pathways related to cell proliferation induced by regular insulin and by four insulin analogs presently approved for therapeutical use. Benign and malignant mammary cell lines showing different insulin receptor (IR) and IGF-I receptor (IGF-IR) expression patterns were studied. Cell proliferation was studied by crystal violet staining (BrdU-FACS analysis). Activation of insulin and IGF signaling pathways was studied by analysis of the phosphorylation status of IGF-IR and of key signaling proteins of the phosphoinositide 3-kinase (PI3K)/Akt and MAP kinase pathways, by the use of specific PI3K and MAP kinase inhibitors, and by silencing of IR and IGF-IR. Lantus stimulated the growth of MCF7 cells, which show high IGF-IR/IR ratio, significantly at 0.3 nmol/l, while regular insulin (Actrapid and bovine insulin) and other insulin analogs (Novorapid, Humalog, and Levemir) stimulated cell growth at 1.5-15 nmol/l concentrations. No difference between Lantus and the other insulin analogs was observed regarding growth stimulation of MCF10A cells showing low IGF-IR/IR ratio. Growth stimulation of MCF7 cells by Lantus was mainly due to strong activation of the IGF-IR and the MAP kinase pathway. Regular insulin and other insulin analogs tested activated mainly the IR and the PI3K/Akt pathway. We conclude that unlike regular insulin and other insulin analogs, Lantus strongly activates the IGF-IR and the MAP kinase pathway in MCF7 cells and is a strong mitogen for cells characterized by a high-IGF-IR/IR ratio.