Effects of insulin-like growth factor I treatment on the molecular distribution of insulin-like growth factors among different binding proteins

1994 ◽  
Vol 83 (s399) ◽  
pp. 159-162 ◽  
Author(s):  
SE Gargosky ◽  
KF Wilson ◽  
PJ Fielder ◽  
MA Vaccarello ◽  
FB Diamond ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Binding Proteins ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Molecular Distribution ◽  
Growth Factor I ◽  
Insulin Like Growth Factors

Role of insulin and insulin-like growth factor I receptor expression in the pathogenesis of genital endometriosis

2021 ◽  
Vol 70 (3) ◽  
pp. 65-74
Author(s):  
Margarita S. Florova ◽  
Maria I. Yarmolinskaya ◽  
Natalya N. Tkachenko ◽  
Gulrukhsor Kh. Tolibova ◽  
Tatyana G. Tral
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Insulin Receptors ◽  
Receptor Expression ◽  
Control Group ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Growth Factor I ◽  
Glucose Stimulated Insulin Secretion ◽  
Insulin Like Growth Factors

BACKGROUND: Growth factors play an important role in the pathogenesis of genital endometriosis. Insulin and insulin-like growth factors are involved in mitosis and differentiation in the endometrium during the menstrual cycle and early pregnancy, and are likely to indirectly affect the invasion of the endometrium during retrograde menstruation and the development of pain syndrome in endometriosis. However, the available literature data on insulin-like growth factors and insulin in the endometrium and endometrioid heterotopies in patients with genital endometriosis are scarse and contradictory. AIM: The aim of this study was to investigate the expression of insulin receptors and insulin-like growth factor I receptors in the eutopic endometrium and endometrioid heterotopies of patients with genital endometriosis. MATERIALS AND METHODS: This cross-sectional study included immunohistochemical analysis of surgical material obtained from two groups of women in the proliferative phase of the menstrual cycle: patients with endometriosis who received surgical treatment (endometrium and endometrioid heterotopies) and patients without endometriosis who were examined due to infertility (endometrium). The study also included investigation of carbohydrate metabolism (glucose tolerance test) and determination of blood serum insulin-like growth factor I, insulin and sex hormone levels. The material was stained to detect the expression of insulin receptors and insulin-like growth factor I receptors. Then, the relative area and optical density of the receptor expression were determined and the obtained data were analyzed statistically. RESULTS: We analyzed the examination results of 131 women matched in age and weight and height characteristics: 101 patients with genital endometriosis and 30 patients in the control group. Carbohydrate metabolism was characterized by a 2.1-fold increase in glucose-stimulated insulin secretion in patients with genital endometriosis compared with the control subjects. The blood level of insulin-like growth factor I did not differ in the study groups. Statistically significant differences in receptor expression were obtained between the groups. In the endometrium of patients with genital endometriosis, the optical density of insulin receptors was lower (p = 0.007) and the expression of insulin-like growth factor I receptors higher (p = 0.002) compared to the endometrium of the control subjects. The median values of insulin receptor expression in endometrioid heterotopies were decreased compared to the endometrium of the control group (p 0.001). The expression of insulin-like growth factor I receptors in endometrioid heterotopies was reduced compared to the endometrium of the same patients (p 0.001). CONCLUSIONS: The data obtained indicate significant features in the functioning of the insulin / insulin-like growth factor I system in patients with genital endometriosis: glucose-stimulated insulin secretion and relative endometrial insulin resistance due to the decreased expression of insulin receptors and the increased expression of insulin-like growth factor I receptors in the endometrium.

Plasma clearance and tissue distribution of labelled insulin-like growth factor-I (IGF-I), IGF-II and des(1–3)IGF-I in rats

1991 ◽  
Vol 128 (2) ◽  
pp. 197-204 ◽  
Author(s):  
F. J. Ballard ◽  
S. E. Knowles ◽  
P. E. Walton ◽  
K. Edson ◽  
P. C. Owens ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Rank Order ◽  
Insulin Like Growth Factor ◽  
Plasma Binding ◽  
Factor I ◽  
Igf I ◽  
The Mean ◽  
Growth Factor I ◽  
Sites Of Action

ABSTRACT Incubation of 125I-labelled insulin-like growth factor-I (IGF-I) with rat plasma at 4 °C led to the transfer of approximately half the radioactivity to 150 kDa and smaller complexes with IGF-binding proteins. The extent of association was greater with labelled IGF-II and essentially absent with the truncated IGF-I analogue, des(1–3)IGF-I. A greater degree of binding of IGF peptides with binding proteins occurred after i.v. injection of the tracers into rats, but most of the des(1–3)IGF-I radioactivity remained free. Measurement of the total plasma clearances showed the rapid removal of des(1–3)IGF-I compared with IGF-I and IGF-II; the mean clearances were 4·59, 1·20 and 1·34 ml/min per kg respectively. The mean steadystate volume of distribution was larger for des(1–3)IGF-I than for IGF-I and IGF-II (461, 167 and 181 ml/kg respectively), probably because of the differences in plasma protein binding. With all tracers, radioactivity appeared in the kidneys to a greater extent than in other organs. The amount of radioactivity found in the adrenals, brain, skin, stomach, duodenum, ileum plus jejunum and colon was in rank order, des(1–3)IGF-I > IGF-I > IGF-II. Since this ranking is the opposite of the abilities of the three IGF peptides to form complexes with plasma binding proteins, we propose that the plasma binding proteins inhibit the transfer of the growth factors to their tissue sites of action. Moreover, we suggest that IGF analogues that are cleared rapidly from blood may have greater biological potencies in vivo. Journal of Endocrinology (1991) 128, 197–204

scholarly journals Phage display-derived ligands provide structural insight into insulin-like growth factor I function

2004 ◽  
Vol 18 (2) ◽  
pp. 237-249
Author(s):  
Nicholas J. Skelton ◽  
Michelle L. Schaffer ◽  
Kurt Deshayes ◽  
Tamas Blandl ◽  
Steven Runyon ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phage Display ◽  
Binding Proteins ◽  
Cell Surface Receptor ◽  
Triple Resonance ◽  
Triple Resonance Nmr ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Insulin–like growth factor–I (IGF–I) is a central mediator of cell growth, differentiation and metabolism. Structural characterization of the protein has been hampered by a combination of internal dynamics and self–association that prevent crystallization and produce broad NMR resonances. To better characterize the functions of IGF–I, we have used phage display to identify peptides that antagonize the binding of IGF–I to its plasma binding proteins (IGFBPs) and cell–surface receptor (IGF–R). Interestingly, binding of peptide improves dramatically the quality of the NMR resonances of IGF–I, and enables the use of triple–resonance NMR methods to characterize the complexes. One such peptide, designated IGF–F1–1, has been studied in detail. In the complex, the peptide retains the same loop–helix motif seen in the free state whilst IGF–I contains three helices, as has been seen previously in low–resolution structures in the absence of ligand. The peptide binds at a hydrophobic patch between helix 1 and 3, a site identified previously by mutagenesis as a contact site for IGFBP1. Thus, antagonism of IGFBP1 binding exhibited by the peptide occurs by a simple steric occlusion mechanism. Antagonism of IGF–R binding may also be explained by a similar mechanism if receptor binding occurs by a two–site process, as has been postulated for insulin binding to its receptor. Comparisons with crystallographic structures determined for IGF–I in other complexes suggest that the region around helix 1 of IGF–I is conformationally conserved whereas the region around helix 3 adopts several different ligand–induced conformations. The ligand–induced structural variability of helix 3 appears to be a common feature across the insulin super–family. In the case of IGF–I, exchange between such conformations may be the source of the dynamic nature of free IGF–I, and likely has functional significance for the ability of IGF–I to recognize two signaling receptors and six binding proteins with high affinity.

scholarly journals Serum and tissue level of insulin-like growth factor-I (IGF-I) and IGF-I binding proteins as an index of pancreatitis and pancreatic cancer

2003 ◽  
Vol 83 (5) ◽  
pp. 239-246 ◽  
Author(s):  
Ewa Karna ◽  
Arkadiusz Surazynski ◽  
Kazimierz Orłowski ◽  
Joanna łaszkiewicz ◽  
Zbigniew Puchalski ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Growth Factor ◽  
Binding Proteins ◽  
Tissue Level ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I
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