Hyperglycemia Regulates the Sensitivity of Vascular Cells to IGF-I Stimulation

2009 ◽  
pp. 11-20
Author(s):  
David R. Clemmons ◽  
Laura A Maile ◽  
Walker H Busby ◽  
Timothy Nichols ◽  
Yan Ling ◽  
...  
Keyword(s):  
Vascular Cells ◽  
Igf I

scholarly journals Identification of Compounds That Inhibit IGF-I Signaling in Hyperglycemia

2009 ◽  
Vol 2009 ◽  
pp. 1-10 ◽  
Author(s):  
Laura A. Maile ◽  
Lee B. Allen ◽  
Umadevi Veluvolu ◽  
Byron E. Capps ◽  
Walker H. Busby ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Transmembrane Protein ◽  
Vascular Complications ◽  
Vascular Cells ◽  
Therapeutic Approaches ◽  
Prevention And Treatment ◽  
Igf I ◽  
Retinal Endothelial Cell ◽  
Endothelial Cell Cultures ◽  
Novel Therapeutic

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.

468: Polymorphic CA Repeats in IGF-I Gene is a Common Genetic Modifier in the Etiology of Prostate Cancer and Benign Prostatic Hyperplasia

2004 ◽  
Vol 171 (4S) ◽  
pp. 125-125
Author(s):  
Lizhong Wang ◽  
Kazunari Sato ◽  
Norihiko Tsuchiya ◽  
Chikara Ohyama ◽  
Shigeru Satoh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Benign Prostatic Hyperplasia ◽  
Genetic Modifier ◽  
Prostatic Hyperplasia ◽  
Igf I ◽  
I Gene

Thrombin Augments Vascular Cell-dependent Migration of Human Mast Cells: Role of MGF

1997 ◽  
Vol 77 (03) ◽  
pp. 577-584 ◽  
Author(s):  
Mehrdad Baghestanian ◽  
Roland Hofbauer ◽  
Hans G Kress ◽  
Johann Wojta ◽  
Astrid Fabry ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mast Cells ◽  
Umbilical Vein ◽  
Vascular Cells ◽  
Migratory Response ◽  
Thrombin Activation ◽  
Umbilical Vein Endothelial Cells ◽  
Primary Tissue ◽  
Local Expression

SummaryRecent data suggest that auricular thrombosis is associated with accumulation of mast cells (MC) in the upper endocardium (where usually no MC reside) and local expression of MGF (mast cell growth factor) (25). In this study, the role of vascular cells, thrombin-activation and MGF, in MC-migration was analyzed. For this purpose, cultured human auricular endocardial cells (HAUEC), umbilical vein endothelial cells (HUVEC) and uterine-(HUTMEC) and skin-derived (HSMEC) microvascular endothelial cells were exposed to thrombin or control medium, and the migration of primary tissue MC (lung, n = 6) and HMC-1 cells (human MC-line) against vascular cells (supernatants) measured. Supernatants (24 h) of unstimulated vascular cells (monolayers of endocardium or endothelium) as well as recombinant (rh) MGF induced a significant migratory response in HMC-1 (control: 3025 ± 344 cells [100 ± 11.4%] vs. MGF, 100 ng/ml: 8806 ± 1019 [291 ± 34%] vs. HAUEC: 9703 ± 1506 [320.8 ± 49.8%] vs. HUTMEC: 8950 ± 1857 [295.9 ± 61.4%] vs. HSMEC: 9965 ± 2018 [329.4 ± 66.7%] vs. HUVEC: 9487 ± 1402 [313.6 ± 46.4%], p <0.05) as well as in primary lung MC. Thrombin-activation (5 U/ml, 12 h) of vascular cells led to an augmentation of the directed migration of MC as well as to a hirudin-sensitive increase in MGF synthesis and release. Moreover, a blocking anti-MGF antibody was found to inhibit MC-migration induced by unstimulated or thrombin-activated vascular cells. Together, these data show that endocardial and other vascular cells can induce migration of human MC. This MC-chemotactic signal of the vasculature is associated with expression and release of MGF, augmentable by thrombin, and may play a role in the pathophysiology of (auricular) thrombosis.

Crosstalk Between PDGF and IGF-I Receptors in Rat Liver Myofibroblasts: Implication for Liver Fibrogenesis

2005 ◽  
Vol 43 (01) ◽  
Author(s):  
R Novosyadlyy ◽  
J Dudas ◽  
A Samoylenko ◽  
G Ramadori ◽  
JG Scharf
Keyword(s):  
Rat Liver ◽  
Liver Myofibroblasts ◽  
Igf I ◽  
Liver Fibrogenesis

Laron syndrome – A case Report

JMS SKIMS ◽  
2017 ◽  
Vol 20 (2) ◽  
pp. 104-106
Author(s):  
Javaid Ahmad Bhat ◽  
Moomin Hussain Bhat ◽  
Hilal Bhat ◽  
Mona Sood ◽  
Shariq Rashid Masoodi
Keyword(s):  
Growth Hormone ◽  
Case Report ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Genetic Disorder ◽  
Female Child ◽  
Receptor Signaling ◽  
Laron Syndrome ◽  
Rare Genetic Disorder ◽  
Igf I

Background : Laron & colleagues (1966) reported a rare genetic disorder in Israliei Jewish sublings which was characterized by insensitivity to growth hormone due to abnormality in growth hormone receptor or post receptor signaling pathway.Case Report: We hereby report a case of a 5 year old female child who presented to us with features similar to Laron syndrome. The diagnosis was made & confirmed by various Lab. investigations like low IGF-I levels and managed accordingly. JMS 2017; 20 (2):104-106  

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