| Characterization of proliferative effects of insulin, insulin analogues and insulin-like growth factor-1 (IGF-1) in human lung fibroblasts. | |
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MedLine Citation:
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PMID: 20924562 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Insulin has been approved for inhaled application, but safety concerns remain, because of un-physiologically high insulin concentrations in the lung. Since insulin may act as growth factor, possible proliferative effects of insulin, insulin analogues and insulin-like growth factor-1 (IGF-1) on human lung fibroblasts were studied. As measure of proliferation [(3)H]-thymidine incorporation was studied in HEL-299, MRC-5, IMR-90 and primary human lung fibroblasts. In all cells, mRNA encoding IGF-1 receptors and two variants of insulin receptors was detected. Insulin and IGF-1 stimulated [(3)H]-thymidine incorporation in all cells. Comparison of the concentration-dependent effects in HEL-299 cells showed that IGF-1 and insulin glargine were more potent (EC(50), 3 and 6 nM) and more effective (maximum increase, by 135-150%) than insulin and insulin detemir (EC(50), 22 and 110 nM; maximum increase: by 80%). Proliferative effects of IGF-1 and insulin were inhibited to the same extent by an antibody (1H7) directed against the IGF-1 receptor α-subunit. Insulin-induced stimulation of [(3)H]-thymidine incorporation was reduced by 83% after siRNA-mediated down-regulation of IGF-1 receptor by about 75%, but not affected by a similar down-regulation of the insulin receptor. Insulin and IGF-1 caused rapid up-regulation of the early genes FOS, EGR-1 and EGR-2 as well as of the gene coding for IGF-1. In conclusion, in human lung fibroblasts insulin exerts marked proliferative effects and the pharmacological profile of this response as well as specific receptor knock-down experiments suggest mediation via IGF-1 receptors. The risk of unwanted structural lung alterations by long-term inhalative application of insulin should be considered. |
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Authors:
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M Warnken; U Reitzenstein; A Sommer; M Fuhrmann; P Mayer; H Enzmann; U R Juergens; K Racké |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-06 |
Journal Detail:
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Title: Naunyn-Schmiedeberg's archives of pharmacology Volume: 382 ISSN: 1432-1912 ISO Abbreviation: Naunyn Schmiedebergs Arch. Pharmacol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0326264 Medline TA: Naunyn Schmiedebergs Arch Pharmacol Country: Germany |
Other Details:
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Languages: eng Pagination: 511-24 Citation Subset: IM |
Affiliation:
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Institute of Pharmacology and Toxicology, University of Bonn, Reuterstraβe 2b, 53113, Bonn, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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