Identification of Compounds That Inhibit IGF-I Signaling in Hyperglycemia
Joint Authors
Allen, Lee B.
Busby, Walker H.
Rowland, Michael
Maile, Laura A.
Clemmons, David R.
Veluvolu, Umadevi
Capps, Byron E.
Source
Experimental Diabetes Research
Issue
Vol. 2009, Issue 2009 (31 Dec. 2009), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2010-01-06
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Increased responsiveness of vascular cells to the growth factor IGF-I has been implicated in complications associated with diabetes.
Here we describe the development of an assay and screening of a library of compounds for their ability to accelerate cleavage of the transmembrane protein integrin-associated protein (IAP) thereby disrupting the association between IAP and SHPS-1 which we have shown as critical for the enhanced response of vascular cells to IGF-I.
The cell-based ELISA utilizes an antibody that specifically detects cleaved, but not intact, IAP.
Of the 1040 compounds tested, 14 were considered active by virtue of their ability to stimulate an increase in antibody-binding indicative of IAP cleavage.
In experiments with smooth muscle and retinal endothelial cell cultures in hyperglycemic conditions, each active compound was shown to accelerate the cleavage of IAP, and this was associated with a decrease in IAP association with SHPS-1 as determined by coimmunoprecipitation of the proteins from cell lysates.
As a consequence of the acceleration in IAP cleavage, the compounds were shown to inhibit IGF-I-stimulated phosphorylation of key signaling molecules including Shc and ERK1/2, and this in turn was associated with a decrease in IGF-I-stimulated cell proliferation.
Identification of these compounds that utilize this mechanism has the potential to yield novel therapeutic approaches for the prevention and treatment of vascular complications associated with diabetes.
American Psychological Association (APA)
Maile, Laura A.& Allen, Lee B.& Veluvolu, Umadevi& Capps, Byron E.& Busby, Walker H.& Rowland, Michael…[et al.]. 2010. Identification of Compounds That Inhibit IGF-I Signaling in Hyperglycemia. Experimental Diabetes Research،Vol. 2009, no. 2009, pp.1-10.
https://search.emarefa.net/detail/BIM-458790
Modern Language Association (MLA)
Maile, Laura A.…[et al.]. Identification of Compounds That Inhibit IGF-I Signaling in Hyperglycemia. Experimental Diabetes Research No. 2009 (2009), pp.1-10.
https://search.emarefa.net/detail/BIM-458790
American Medical Association (AMA)
Maile, Laura A.& Allen, Lee B.& Veluvolu, Umadevi& Capps, Byron E.& Busby, Walker H.& Rowland, Michael…[et al.]. Identification of Compounds That Inhibit IGF-I Signaling in Hyperglycemia. Experimental Diabetes Research. 2010. Vol. 2009, no. 2009, pp.1-10.
https://search.emarefa.net/detail/BIM-458790
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-458790