Structural characterisation of the insulin-like growth factor (IGF) binding proteins and IGF receptors, their interactions with other physiological molecules and alterations in metabolic disorders

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Structural characterisation of the insulin-like growth factor (IGF) binding proteins and IGF receptors, their interactions with other physiological molecules and alterations in metabolic disorders (en)
Структурне карактеристике везујућих протеина и рецептора за инсулину сличне факторе раста (IGF), њихове интеракције са другим физиолошким молекулима и промене код поремећаја метаболизма (sr)
Strukturne karakteristike vezujućih proteina i receptora za insulinu slične faktore rasta (IGF), njihove interakcije sa drugim fiziološkim molekulima i promene kod poremećaja metabolizma (sr_RS)
Authors

Publications

Effect of Hyperbaric Oxygen Therapy on Fatty Acid Composition and Insulin-like Growth Factor Binding Protein 1 in Adult Type 1 Diabetes Mellitus Patients: A Pilot Study

Resanović, Ivana; Gluvić, Zoran; Zarić, Božidarka; Sudar-Milovanović, Emina; Vučić, Vesna; Arsić, Aleksandra; Nedić, Olgica; Šunderić, Miloš; Gligorijević, Nikola; Milačić, Davorka; Isenović, Esma R.

(2020)

TY  - JOUR
AU  - Resanović, Ivana
AU  - Gluvić, Zoran
AU  - Zarić, Božidarka
AU  - Sudar-Milovanović, Emina
AU  - Vučić, Vesna
AU  - Arsić, Aleksandra
AU  - Nedić, Olgica
AU  - Šunderić, Miloš
AU  - Gligorijević, Nikola
AU  - Milačić, Davorka
AU  - Isenović, Esma R.
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8567
AB  - Objective: Metabolic changes in insulin-dependent diabetes mellitus (IDDM) impair vasodilation, and this leads to tissue hypoxia and microvascular pathology. Hyperbaric oxygen therapy (HBOT) can significantly improve the outcome of ischemic conditions in IDDM patients and reduce vascular complications. The aim of our study was to assess the effects of HBOT on plasma fatty acid (FA) composition, and expression of insulin-like growth factor binding protein 1 (IGFBP-1) in IDDM patients. Methods: Our study included 24 adult IDDM patients diagnosed with peripheral vascular complications. The patients were exposed to 10 sessions of 100% oxygen inhalation at 2.4 atmosphere absolute for 1 hour. Blood samples were collected at admission and after HBOT for measurement of metabolic parameters, FA composition and IGFBP-1. Measurement of plasma FA composition was determined by gas chromatography. Expression of IGFBP-1 in the serum was estimated by Western blot analysis. Results: HBOT decreased blood levels of total cholesterol (p<0.05), triglycerides (p<0.05) and low-density lipoprotein (p<0.05). HBOT increased plasma levels of individual FAs: palmitic acid (p<0.05), palmitoleic acid (p<0.05), docosapentaenoic acid (p<0.05) and docosahexaenoic acid (p<0.01), and decreased levels of stearic acid (p<0.05), alpha linolenic acid (p<0.05) and linoleic acid (p<0.01). Expression of IGFBP-1 (p<0.01) was increased, whereas the level of insulin (p<0.001) was decreased in the serum after HBOT. Conclusions: Our results indicate that HBOT exerts beneficial effects in IDDM patients by improving the lipid profile and altering FA composition. © 2019 Canadian Diabetes Association
T2  - Canadian Journal of Diabetes
T1  - Effect of Hyperbaric Oxygen Therapy on Fatty Acid Composition and Insulin-like Growth Factor Binding Protein 1 in Adult Type 1 Diabetes Mellitus Patients: A Pilot Study
VL  - 44
IS  - 1
SP  - 22
EP  - 29
DO  - 10.1016/j.jcjd.2019.04.018
ER  - 
@article{
author = "Resanović, Ivana and Gluvić, Zoran and Zarić, Božidarka and Sudar-Milovanović, Emina and Vučić, Vesna and Arsić, Aleksandra and Nedić, Olgica and Šunderić, Miloš and Gligorijević, Nikola and Milačić, Davorka and Isenović, Esma R.",
year = "2020",
abstract = "Objective: Metabolic changes in insulin-dependent diabetes mellitus (IDDM) impair vasodilation, and this leads to tissue hypoxia and microvascular pathology. Hyperbaric oxygen therapy (HBOT) can significantly improve the outcome of ischemic conditions in IDDM patients and reduce vascular complications. The aim of our study was to assess the effects of HBOT on plasma fatty acid (FA) composition, and expression of insulin-like growth factor binding protein 1 (IGFBP-1) in IDDM patients. Methods: Our study included 24 adult IDDM patients diagnosed with peripheral vascular complications. The patients were exposed to 10 sessions of 100% oxygen inhalation at 2.4 atmosphere absolute for 1 hour. Blood samples were collected at admission and after HBOT for measurement of metabolic parameters, FA composition and IGFBP-1. Measurement of plasma FA composition was determined by gas chromatography. Expression of IGFBP-1 in the serum was estimated by Western blot analysis. Results: HBOT decreased blood levels of total cholesterol (p<0.05), triglycerides (p<0.05) and low-density lipoprotein (p<0.05). HBOT increased plasma levels of individual FAs: palmitic acid (p<0.05), palmitoleic acid (p<0.05), docosapentaenoic acid (p<0.05) and docosahexaenoic acid (p<0.01), and decreased levels of stearic acid (p<0.05), alpha linolenic acid (p<0.05) and linoleic acid (p<0.01). Expression of IGFBP-1 (p<0.01) was increased, whereas the level of insulin (p<0.001) was decreased in the serum after HBOT. Conclusions: Our results indicate that HBOT exerts beneficial effects in IDDM patients by improving the lipid profile and altering FA composition. © 2019 Canadian Diabetes Association",
journal = "Canadian Journal of Diabetes",
title = "Effect of Hyperbaric Oxygen Therapy on Fatty Acid Composition and Insulin-like Growth Factor Binding Protein 1 in Adult Type 1 Diabetes Mellitus Patients: A Pilot Study",
volume = "44",
number = "1",
pages = "22-29",
doi = "10.1016/j.jcjd.2019.04.018"
}
Resanović, I., Gluvić, Z., Zarić, B., Sudar-Milovanović, E., Vučić, V., Arsić, A., Nedić, O., Šunderić, M., Gligorijević, N., Milačić, D.,& Isenović, E. R.. (2020). Effect of Hyperbaric Oxygen Therapy on Fatty Acid Composition and Insulin-like Growth Factor Binding Protein 1 in Adult Type 1 Diabetes Mellitus Patients: A Pilot Study. in Canadian Journal of Diabetes, 44(1), 22-29.
https://doi.org/10.1016/j.jcjd.2019.04.018
Resanović I, Gluvić Z, Zarić B, Sudar-Milovanović E, Vučić V, Arsić A, Nedić O, Šunderić M, Gligorijević N, Milačić D, Isenović ER. Effect of Hyperbaric Oxygen Therapy on Fatty Acid Composition and Insulin-like Growth Factor Binding Protein 1 in Adult Type 1 Diabetes Mellitus Patients: A Pilot Study. in Canadian Journal of Diabetes. 2020;44(1):22-29.
doi:10.1016/j.jcjd.2019.04.018 .
Resanović, Ivana, Gluvić, Zoran, Zarić, Božidarka, Sudar-Milovanović, Emina, Vučić, Vesna, Arsić, Aleksandra, Nedić, Olgica, Šunderić, Miloš, Gligorijević, Nikola, Milačić, Davorka, Isenović, Esma R., "Effect of Hyperbaric Oxygen Therapy on Fatty Acid Composition and Insulin-like Growth Factor Binding Protein 1 in Adult Type 1 Diabetes Mellitus Patients: A Pilot Study" in Canadian Journal of Diabetes, 44, no. 1 (2020):22-29,
https://doi.org/10.1016/j.jcjd.2019.04.018 . .
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Preeclampsia transforms membrane N-glycome in human placenta

Robajac, Dragana; Vanhooren, Valerie; Masnikosa, Romana; Miković, Zeljko; Mandić, Vesna; Libert, Claude; Nedić, Olgica

(Elsevier, 2016)

TY  - JOUR
AU  - Robajac, Dragana
AU  - Vanhooren, Valerie
AU  - Masnikosa, Romana
AU  - Miković, Zeljko
AU  - Mandić, Vesna
AU  - Libert, Claude
AU  - Nedić, Olgica
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/934
AB  - Posttranslational modifications (PTM) which accompany pathological conditions affect protein structure, characteristics and modulate its activity. Glycosylation is one of the most frequent PTM influencing protein folding, localisation and function. Hypertension is a common gestational complication, which can lead to foetal growth restriction (IUGR) and even to foetal or maternal death. In this work we focused on the impact of preeclampsia complicated with IUGR on placental membrane N-glycome. Results have shown that preeclampsia reduced fucosylation of placental glycans, increased the appearance of paucimannosidic and mannosidic structures with lower number of mannose residues and decreased the amount of glycans with more mannose residues. Since preeclampsia is tightly connected to IUGR, glycosylation changes were investigated also on the functional membrane receptors responsible for growth: insulin receptor and the type 1 insulin-like growth factor receptor (IR and IGF1R). It was found that IR present in the IUGR placenta contained significantly less alpha 2,6-Sia. Therefore, glycans on placental membranes alter due to preeclampsia, but changes seen at the level of the entire N-glycome may be different from the changes detected at the level of a specific glycoprotein. The difference recorded due to pathology in one membrane molecule (IR) was not found in another homologous molecule (IGF1R). Thus, besides studying the glycosylation pattern of the entire placental membrane due to preeclampsia, it is inevitable to study directly glycoprotein of interest, as no general assumptions or extrapolations can be made. (C) 2015 Elsevier Inc All rights reserved.
PB  - Elsevier
T2  - Experimental and Molecular Pathology
T1  - Preeclampsia transforms membrane N-glycome in human placenta
VL  - 100
IS  - 1
SP  - 26
EP  - 30
DO  - 10.1016/j.yexmp.2015.11.029
ER  - 
@article{
author = "Robajac, Dragana and Vanhooren, Valerie and Masnikosa, Romana and Miković, Zeljko and Mandić, Vesna and Libert, Claude and Nedić, Olgica",
year = "2016",
abstract = "Posttranslational modifications (PTM) which accompany pathological conditions affect protein structure, characteristics and modulate its activity. Glycosylation is one of the most frequent PTM influencing protein folding, localisation and function. Hypertension is a common gestational complication, which can lead to foetal growth restriction (IUGR) and even to foetal or maternal death. In this work we focused on the impact of preeclampsia complicated with IUGR on placental membrane N-glycome. Results have shown that preeclampsia reduced fucosylation of placental glycans, increased the appearance of paucimannosidic and mannosidic structures with lower number of mannose residues and decreased the amount of glycans with more mannose residues. Since preeclampsia is tightly connected to IUGR, glycosylation changes were investigated also on the functional membrane receptors responsible for growth: insulin receptor and the type 1 insulin-like growth factor receptor (IR and IGF1R). It was found that IR present in the IUGR placenta contained significantly less alpha 2,6-Sia. Therefore, glycans on placental membranes alter due to preeclampsia, but changes seen at the level of the entire N-glycome may be different from the changes detected at the level of a specific glycoprotein. The difference recorded due to pathology in one membrane molecule (IR) was not found in another homologous molecule (IGF1R). Thus, besides studying the glycosylation pattern of the entire placental membrane due to preeclampsia, it is inevitable to study directly glycoprotein of interest, as no general assumptions or extrapolations can be made. (C) 2015 Elsevier Inc All rights reserved.",
publisher = "Elsevier",
journal = "Experimental and Molecular Pathology",
title = "Preeclampsia transforms membrane N-glycome in human placenta",
volume = "100",
number = "1",
pages = "26-30",
doi = "10.1016/j.yexmp.2015.11.029"
}
Robajac, D., Vanhooren, V., Masnikosa, R., Miković, Z., Mandić, V., Libert, C.,& Nedić, O.. (2016). Preeclampsia transforms membrane N-glycome in human placenta. in Experimental and Molecular Pathology
Elsevier., 100(1), 26-30.
https://doi.org/10.1016/j.yexmp.2015.11.029
Robajac D, Vanhooren V, Masnikosa R, Miković Z, Mandić V, Libert C, Nedić O. Preeclampsia transforms membrane N-glycome in human placenta. in Experimental and Molecular Pathology. 2016;100(1):26-30.
doi:10.1016/j.yexmp.2015.11.029 .
Robajac, Dragana, Vanhooren, Valerie, Masnikosa, Romana, Miković, Zeljko, Mandić, Vesna, Libert, Claude, Nedić, Olgica, "Preeclampsia transforms membrane N-glycome in human placenta" in Experimental and Molecular Pathology, 100, no. 1 (2016):26-30,
https://doi.org/10.1016/j.yexmp.2015.11.029 . .
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Gestation-associated changes in the glycosylation of placental insulin and insulin-like growth factor receptors

Robajac, Dragana; Masnikosa, Romana; Miković, Zeljko; Nedić, Olgica

(Elsevier, 2016)

TY  - JOUR
AU  - Robajac, Dragana
AU  - Masnikosa, Romana
AU  - Miković, Zeljko
AU  - Nedić, Olgica
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/994
AB  - Introduction: Insulin receptor (IR) and type 1 and type 2 insulin-like growth factor receptors (IGF1 R and IGF2R) play important roles in regulation of placental and foetal growth. All three receptors are abundantly glycosylated. N-glycosylation significantly affects protein conformation and may alter its function. We have recently found that the N-glycome of placental membrane proteins alters during gestation. The aim of the study presented herein was to investigate whether there were gestation-related changes in N-glycan profiles of placental IR and IGFRs. Methods: Placentas from healthy women at first (FTP) and third trimester (TTP) of pregnancy were collected, membrane proteins isolated, solubilised and used as the source of IR and IGFRs. Reactivity of glycoforms of IR and IGFRs with lectins was monitored by measuring radioactivity of I-125-ligands-receptors complexes. Results: Significant differences in the binding pattern of all three receptors to the lectins were observed between FTP and TTP, which suggest gestational changes in N-glycans bound to receptors. These changes include decrease in total fucosylated, core-fucosylated biantennary N-glycan (NA2F) and alpha 2,6-sialo-N-glycans (for IR); decrease in total fucosylated and a2,6-sialo-N-glycans and an increase in NA2F N-glycans (for IGF1R) and an increase in the total fucosylation and NA2F N-glycans (for IGF2R). Discussion: The gestational alterations in N-glycans attached to IR and IGFRs may represent a mechanism by which these receptors acquire new/additional roles as gestation progresses. (C) 2016 Elsevier Ltd. All rights reserved.
PB  - Elsevier
T2  - Placenta
T1  - Gestation-associated changes in the glycosylation of placental insulin and insulin-like growth factor receptors
VL  - 39
SP  - 70
EP  - 76
DO  - 10.1016/j.placenta.2016.01.005
ER  - 
@article{
author = "Robajac, Dragana and Masnikosa, Romana and Miković, Zeljko and Nedić, Olgica",
year = "2016",
abstract = "Introduction: Insulin receptor (IR) and type 1 and type 2 insulin-like growth factor receptors (IGF1 R and IGF2R) play important roles in regulation of placental and foetal growth. All three receptors are abundantly glycosylated. N-glycosylation significantly affects protein conformation and may alter its function. We have recently found that the N-glycome of placental membrane proteins alters during gestation. The aim of the study presented herein was to investigate whether there were gestation-related changes in N-glycan profiles of placental IR and IGFRs. Methods: Placentas from healthy women at first (FTP) and third trimester (TTP) of pregnancy were collected, membrane proteins isolated, solubilised and used as the source of IR and IGFRs. Reactivity of glycoforms of IR and IGFRs with lectins was monitored by measuring radioactivity of I-125-ligands-receptors complexes. Results: Significant differences in the binding pattern of all three receptors to the lectins were observed between FTP and TTP, which suggest gestational changes in N-glycans bound to receptors. These changes include decrease in total fucosylated, core-fucosylated biantennary N-glycan (NA2F) and alpha 2,6-sialo-N-glycans (for IR); decrease in total fucosylated and a2,6-sialo-N-glycans and an increase in NA2F N-glycans (for IGF1R) and an increase in the total fucosylation and NA2F N-glycans (for IGF2R). Discussion: The gestational alterations in N-glycans attached to IR and IGFRs may represent a mechanism by which these receptors acquire new/additional roles as gestation progresses. (C) 2016 Elsevier Ltd. All rights reserved.",
publisher = "Elsevier",
journal = "Placenta",
title = "Gestation-associated changes in the glycosylation of placental insulin and insulin-like growth factor receptors",
volume = "39",
pages = "70-76",
doi = "10.1016/j.placenta.2016.01.005"
}
Robajac, D., Masnikosa, R., Miković, Z.,& Nedić, O.. (2016). Gestation-associated changes in the glycosylation of placental insulin and insulin-like growth factor receptors. in Placenta
Elsevier., 39, 70-76.
https://doi.org/10.1016/j.placenta.2016.01.005
Robajac D, Masnikosa R, Miković Z, Nedić O. Gestation-associated changes in the glycosylation of placental insulin and insulin-like growth factor receptors. in Placenta. 2016;39:70-76.
doi:10.1016/j.placenta.2016.01.005 .
Robajac, Dragana, Masnikosa, Romana, Miković, Zeljko, Nedić, Olgica, "Gestation-associated changes in the glycosylation of placental insulin and insulin-like growth factor receptors" in Placenta, 39 (2016):70-76,
https://doi.org/10.1016/j.placenta.2016.01.005 . .
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Oxidation of placental insulin and insulin-like growth factor receptors in mothers with diabetes mellitus or preeclampsia complicated with intrauterine growth restriction

Robajac, D.; Masnikosa, Romana; Mikovic, Z.; Mandie, V.; Nedić, Olgica

(2015)

TY  - JOUR
AU  - Robajac, D.
AU  - Masnikosa, Romana
AU  - Mikovic, Z.
AU  - Mandie, V.
AU  - Nedić, Olgica
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/721
AB  - Placental insulin receptor (IR) and insulin-like growth factor receptors (IGFRs) are essential for fetal growth. We investigated structural changes of these receptors exposed to increased oxidative stress in mothers diagnosed with diabetes mellitus (DM) or preeclampsia (PE) complicated with intrauterine growth restriction. Increased amount of IR and decreased amounts of IGF1R and IGF2R were found in both pathologies, accompanied by significant elevation in protein carbonyls. When isolated receptors were examined, increased carbonylation of IR and IGF1R in PE placentas was detected, whereas the amounts of carbonylated IR and IGF1R were similar in DM and healthy placentas. Carbonylation status of IGF2R did not change due to pathology, confirming the detrimental role of primary structure and conformation in oxidative susceptibility. Ligand binding was similar in all three groups of samples and did not seem to be affected by receptor oxidation. Since babies delivered by mothers with PE were smaller than the referent population, increased carbonylation of receptors might have affected downstream receptor signaling post-ligand binding.
T2  - Free Radical Research
T1  - Oxidation of placental insulin and insulin-like growth factor receptors in mothers with diabetes mellitus or preeclampsia complicated with intrauterine growth restriction
VL  - 49
IS  - 8
SP  - 984
EP  - 989
DO  - 10.3109/10715762.2015.1020798
ER  - 
@article{
author = "Robajac, D. and Masnikosa, Romana and Mikovic, Z. and Mandie, V. and Nedić, Olgica",
year = "2015",
abstract = "Placental insulin receptor (IR) and insulin-like growth factor receptors (IGFRs) are essential for fetal growth. We investigated structural changes of these receptors exposed to increased oxidative stress in mothers diagnosed with diabetes mellitus (DM) or preeclampsia (PE) complicated with intrauterine growth restriction. Increased amount of IR and decreased amounts of IGF1R and IGF2R were found in both pathologies, accompanied by significant elevation in protein carbonyls. When isolated receptors were examined, increased carbonylation of IR and IGF1R in PE placentas was detected, whereas the amounts of carbonylated IR and IGF1R were similar in DM and healthy placentas. Carbonylation status of IGF2R did not change due to pathology, confirming the detrimental role of primary structure and conformation in oxidative susceptibility. Ligand binding was similar in all three groups of samples and did not seem to be affected by receptor oxidation. Since babies delivered by mothers with PE were smaller than the referent population, increased carbonylation of receptors might have affected downstream receptor signaling post-ligand binding.",
journal = "Free Radical Research",
title = "Oxidation of placental insulin and insulin-like growth factor receptors in mothers with diabetes mellitus or preeclampsia complicated with intrauterine growth restriction",
volume = "49",
number = "8",
pages = "984-989",
doi = "10.3109/10715762.2015.1020798"
}
Robajac, D., Masnikosa, R., Mikovic, Z., Mandie, V.,& Nedić, O.. (2015). Oxidation of placental insulin and insulin-like growth factor receptors in mothers with diabetes mellitus or preeclampsia complicated with intrauterine growth restriction. in Free Radical Research, 49(8), 984-989.
https://doi.org/10.3109/10715762.2015.1020798
Robajac D, Masnikosa R, Mikovic Z, Mandie V, Nedić O. Oxidation of placental insulin and insulin-like growth factor receptors in mothers with diabetes mellitus or preeclampsia complicated with intrauterine growth restriction. in Free Radical Research. 2015;49(8):984-989.
doi:10.3109/10715762.2015.1020798 .
Robajac, D., Masnikosa, Romana, Mikovic, Z., Mandie, V., Nedić, Olgica, "Oxidation of placental insulin and insulin-like growth factor receptors in mothers with diabetes mellitus or preeclampsia complicated with intrauterine growth restriction" in Free Radical Research, 49, no. 8 (2015):984-989,
https://doi.org/10.3109/10715762.2015.1020798 . .
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