Insulin-like growth factor binding protein production in bovine retinal endothelial cells

Metabolism: Clinical and Experimental
S GianniniC M Rotella

Abstract

Retinopathy is the most frequent microangiopathic complication in diabetes. Many circulating hormones and locally produced mitogenic factors have been involved. Bovine retinal endothelial cells (BRECs) were cultured to investigate if insulin, insulin-like growth factors (IGFs), IGF binding proteins (IGFBPs), and a chronic high-glucose condition could control endothelial cell growth. Specific IGF-I receptors with two binding sites with high (Kd 0.03 nmol/L) and low (Kd 1.3 nmol/L) affinity were found when analyzing families of displacement curves between IGF-I versus IGF-I and IGF-I versus insulin. However, IGFs failed to be mitogenic factors in these cells. This could be explained by an inhibitory effect due to the presence of specific IGFBPs with a molecular weight between 24 and 43 kd. Using Western blot and immunoblot analysis, Northern blot study, and specific radioimmunoassay (RIA), these IGFBPs have been identified as IGFBP-3, -2, -5, and -4. Insulin, which does not bind to IGFBPs, was a potent mitogenic factor in these cells at a high concentration (10 nmol/L), suggesting a cross-reaction to IGF-I receptor. These IGFBPs, except the 24-kd form (IGFBP-4), were modulated by both IGF-I and IGF-II, with a maximum effect at 10...Continue Reading

References

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Citations

Jan 29, 2000·Clinical Endocrinology·J A Janssen, S W Lamberts
Jan 31, 2002·Journal of Endocrinological Investigation·L PalaC M Rotella
Feb 1, 2018·Expert Opinion on Drug Discovery·Goldis MalekMayur Choudhary
Oct 6, 1999·Molecular and Cellular Endocrinology·S GianniniC M Rotella

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