Obradović, Milan

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  • Obradović, Milan (4)

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The involvement of Akt, mTOR, and S6K in the in vivo effect of IGF-1 on the regulation of rat cardiac Na+/K+-ATPase

Banjac, Katarina; Obradović, Milan; Zafirović, Sonja; Essack, Magbubah; Gluvić, Zoran; Šunderić, Miloš; Nedić, Olgica; Isenović, Esma R.

(2024)

TY  - JOUR
AU  - Banjac, Katarina
AU  - Obradović, Milan
AU  - Zafirović, Sonja
AU  - Essack, Magbubah
AU  - Gluvić, Zoran
AU  - Šunderić, Miloš
AU  - Nedić, Olgica
AU  - Isenović, Esma R.
PY  - 2024
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/13184
AB  - Background We previously demonstrated that insulin-like growth factor-1 (IGF-1) regulates sodium/potassium adenosine triphosphatase (Na+/K+-ATPase) in vascular smooth muscle cells (VSMC) via phosphatidylinositol-3 kinase (PI3K). Taking into account that others’ work show that IGF-1 activates the PI3K/protein kinase B (Akt) signaling pathway in many different cells, we here further questioned if the Akt/mammalian target of rapamycin (mTOR)/ribosomal protein p70 S6 kinase (S6K) pathway stimulates Na+/K+-ATPase, an essential protein for maintaining normal heart function. Methods and results There were 14 adult male Wistar rats, half of whom received bolus injections of IGF-1 (50 μg/kg) for 24 h. We evaluated cardiac Na+/K+-ATPase expression, activity, and serum IGF-1 levels. Additionally, we examined the phosphorylated forms of the following proteins: insulin receptor substrate (IRS), phosphoinositide-dependent kinase-1 (PDK-1), Akt, mTOR, S6K, and α subunit of Na+/K+-ATPase. Additionally, the mRNA expression of the Na+/K+-ATPase α1 subunit was evaluated. Treatment with IGF-1 increases levels of serum IGF-1 and stimulates Na+/K+-ATPase activity, phosphorylation of α subunit of Na+/K+-ATPase on Ser23, and protein expression of α2 subunit. Furthermore, IGF-1 treatment increased phosphorylation of IRS-1 on Tyr1222, Akt on Ser473, PDK-1 on Ser241, mTOR on Ser2481 and Ser2448, and S6K on Thr421/Ser424. The concentration of IGF-1 in serum positively correlates with Na+/K+-ATPase activity and the phosphorylated form of mTOR (Ser2448), while Na+/K+-ATPase activity positively correlates with the phosphorylated form of IRS-1 (Tyr1222) and mTOR (Ser2448). Conclusion These results indicate that the Akt/mTOR/S6K signalling pathway may be involved in the IGF-1 regulating cardiac Na+/K+-ATPase expression and activity
T2  - Molecular Biology Reports
T1  - The involvement of Akt, mTOR, and S6K in the in vivo effect of IGF-1 on the regulation of rat cardiac Na+/K+-ATPase
VL  - 51
IS  - 1
DO  - 10.1007/s11033-024-09451-3
ER  - 
@article{
author = "Banjac, Katarina and Obradović, Milan and Zafirović, Sonja and Essack, Magbubah and Gluvić, Zoran and Šunderić, Miloš and Nedić, Olgica and Isenović, Esma R.",
year = "2024",
abstract = "Background We previously demonstrated that insulin-like growth factor-1 (IGF-1) regulates sodium/potassium adenosine triphosphatase (Na+/K+-ATPase) in vascular smooth muscle cells (VSMC) via phosphatidylinositol-3 kinase (PI3K). Taking into account that others’ work show that IGF-1 activates the PI3K/protein kinase B (Akt) signaling pathway in many different cells, we here further questioned if the Akt/mammalian target of rapamycin (mTOR)/ribosomal protein p70 S6 kinase (S6K) pathway stimulates Na+/K+-ATPase, an essential protein for maintaining normal heart function. Methods and results There were 14 adult male Wistar rats, half of whom received bolus injections of IGF-1 (50 μg/kg) for 24 h. We evaluated cardiac Na+/K+-ATPase expression, activity, and serum IGF-1 levels. Additionally, we examined the phosphorylated forms of the following proteins: insulin receptor substrate (IRS), phosphoinositide-dependent kinase-1 (PDK-1), Akt, mTOR, S6K, and α subunit of Na+/K+-ATPase. Additionally, the mRNA expression of the Na+/K+-ATPase α1 subunit was evaluated. Treatment with IGF-1 increases levels of serum IGF-1 and stimulates Na+/K+-ATPase activity, phosphorylation of α subunit of Na+/K+-ATPase on Ser23, and protein expression of α2 subunit. Furthermore, IGF-1 treatment increased phosphorylation of IRS-1 on Tyr1222, Akt on Ser473, PDK-1 on Ser241, mTOR on Ser2481 and Ser2448, and S6K on Thr421/Ser424. The concentration of IGF-1 in serum positively correlates with Na+/K+-ATPase activity and the phosphorylated form of mTOR (Ser2448), while Na+/K+-ATPase activity positively correlates with the phosphorylated form of IRS-1 (Tyr1222) and mTOR (Ser2448). Conclusion These results indicate that the Akt/mTOR/S6K signalling pathway may be involved in the IGF-1 regulating cardiac Na+/K+-ATPase expression and activity",
journal = "Molecular Biology Reports",
title = "The involvement of Akt, mTOR, and S6K in the in vivo effect of IGF-1 on the regulation of rat cardiac Na+/K+-ATPase",
volume = "51",
number = "1",
doi = "10.1007/s11033-024-09451-3"
}
Banjac, K., Obradović, M., Zafirović, S., Essack, M., Gluvić, Z., Šunderić, M., Nedić, O.,& Isenović, E. R.. (2024). The involvement of Akt, mTOR, and S6K in the in vivo effect of IGF-1 on the regulation of rat cardiac Na+/K+-ATPase. in Molecular Biology Reports, 51(1).
https://doi.org/10.1007/s11033-024-09451-3
Banjac K, Obradović M, Zafirović S, Essack M, Gluvić Z, Šunderić M, Nedić O, Isenović ER. The involvement of Akt, mTOR, and S6K in the in vivo effect of IGF-1 on the regulation of rat cardiac Na+/K+-ATPase. in Molecular Biology Reports. 2024;51(1).
doi:10.1007/s11033-024-09451-3 .
Banjac, Katarina, Obradović, Milan, Zafirović, Sonja, Essack, Magbubah, Gluvić, Zoran, Šunderić, Miloš, Nedić, Olgica, Isenović, Esma R., "The involvement of Akt, mTOR, and S6K in the in vivo effect of IGF-1 on the regulation of rat cardiac Na+/K+-ATPase" in Molecular Biology Reports, 51, no. 1 (2024),
https://doi.org/10.1007/s11033-024-09451-3 . .

Could the level of nitrite/nitrate contribute to malignant thyroid nodule diagnostics?

Samardžić, Vladimir; Banjac, Katarina; Obradović, Milan; Gluvić, Zoran; Isenović, Esma R.

(2021)

TY  - JOUR
AU  - Samardžić, Vladimir
AU  - Banjac, Katarina
AU  - Obradović, Milan
AU  - Gluvić, Zoran
AU  - Isenović, Esma R.
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9697
AB  - Thyroid nodules are among highly prevalent thyroid diseases. To make a distinction between benign and malignant thyroid nodules are of cumbersome significance for each endocrinologist. There is no unique and completely accurate diagnostic test, method, or even biomarker that points to a malignant thyroid nodule. Many studies in modern thyroidology are conducted to determine the usefulness of individual biomarkers, which could help clinicians detect thyroid nodules' potential malignant nature. One interesting biomarker with a promising diagnostic potential for the thyroid gland pathological conditions is nitric oxide (NO). Inducible nitric oxide synthase expression is increased in thyroiditis cases and even more in thyroid carcinoma cases, directly connected with increased NO levels in both pathological conditions. We hypothesize that the basal levels of nitrite/nitrate in serum and biopsy washout could indicate nodules' malignant nature.
T2  - Medical Hypotheses
T1  - Could the level of nitrite/nitrate contribute to malignant thyroid nodule diagnostics?
VL  - 150
SP  - 110569
DO  - 10.1016/j.mehy.2021.110569
ER  - 
@article{
author = "Samardžić, Vladimir and Banjac, Katarina and Obradović, Milan and Gluvić, Zoran and Isenović, Esma R.",
year = "2021",
abstract = "Thyroid nodules are among highly prevalent thyroid diseases. To make a distinction between benign and malignant thyroid nodules are of cumbersome significance for each endocrinologist. There is no unique and completely accurate diagnostic test, method, or even biomarker that points to a malignant thyroid nodule. Many studies in modern thyroidology are conducted to determine the usefulness of individual biomarkers, which could help clinicians detect thyroid nodules' potential malignant nature. One interesting biomarker with a promising diagnostic potential for the thyroid gland pathological conditions is nitric oxide (NO). Inducible nitric oxide synthase expression is increased in thyroiditis cases and even more in thyroid carcinoma cases, directly connected with increased NO levels in both pathological conditions. We hypothesize that the basal levels of nitrite/nitrate in serum and biopsy washout could indicate nodules' malignant nature.",
journal = "Medical Hypotheses",
title = "Could the level of nitrite/nitrate contribute to malignant thyroid nodule diagnostics?",
volume = "150",
pages = "110569",
doi = "10.1016/j.mehy.2021.110569"
}
Samardžić, V., Banjac, K., Obradović, M., Gluvić, Z.,& Isenović, E. R.. (2021). Could the level of nitrite/nitrate contribute to malignant thyroid nodule diagnostics?. in Medical Hypotheses, 150, 110569.
https://doi.org/10.1016/j.mehy.2021.110569
Samardžić V, Banjac K, Obradović M, Gluvić Z, Isenović ER. Could the level of nitrite/nitrate contribute to malignant thyroid nodule diagnostics?. in Medical Hypotheses. 2021;150:110569.
doi:10.1016/j.mehy.2021.110569 .
Samardžić, Vladimir, Banjac, Katarina, Obradović, Milan, Gluvić, Zoran, Isenović, Esma R., "Could the level of nitrite/nitrate contribute to malignant thyroid nodule diagnostics?" in Medical Hypotheses, 150 (2021):110569,
https://doi.org/10.1016/j.mehy.2021.110569 . .
1
1

Leptin and Obesity: Role and Clinical Implication

Obradović, Milan; Sudar-Milovanović, Emina; Soskić, Sanja S.; Essack, Magbubah; Arya, Swati; Stewart, Alan J.; Gojobori, Takashi; Isenović, Esma R.

(2021)

TY  - JOUR
AU  - Obradović, Milan
AU  - Sudar-Milovanović, Emina
AU  - Soskić, Sanja S.
AU  - Essack, Magbubah
AU  - Arya, Swati
AU  - Stewart, Alan J.
AU  - Gojobori, Takashi
AU  - Isenović, Esma R.
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9833
AB  - The peptide hormone leptin regulates food intake, body mass, and reproductive function and plays a role in fetal growth, proinflammatory immune responses, angiogenesis and lipolysis. Leptin is a product of the obese (ob) gene and, following synthesis and secretion from fat cells in white adipose tissue, binds to and activates its cognate receptor, the leptin receptor (LEP-R). LEP-R distribution facilitates leptin’s pleiotropic effects, playing a crucial role in regulating body mass via a negative feedback mechanism between adipose tissue and the hypothalamus. Leptin resistance is characterized by reduced satiety, over-consumption of nutrients, and increased total body mass. Often this leads to obesity, which reduces the effectiveness of using exogenous leptin as a therapeutic agent. Thus, combining leptin therapies with leptin sensitizers may help overcome such resistance and, consequently, obesity. This review examines recent data obtained from human and animal studies related to leptin, its role in obesity, and its usefulness in obesity treatment.
T2  - Frontiers in Endocrinology
T1  - Leptin and Obesity: Role and Clinical Implication
VL  - 12
SP  - 563
DO  - 10.3389/fendo.2021.585887
ER  - 
@article{
author = "Obradović, Milan and Sudar-Milovanović, Emina and Soskić, Sanja S. and Essack, Magbubah and Arya, Swati and Stewart, Alan J. and Gojobori, Takashi and Isenović, Esma R.",
year = "2021",
abstract = "The peptide hormone leptin regulates food intake, body mass, and reproductive function and plays a role in fetal growth, proinflammatory immune responses, angiogenesis and lipolysis. Leptin is a product of the obese (ob) gene and, following synthesis and secretion from fat cells in white adipose tissue, binds to and activates its cognate receptor, the leptin receptor (LEP-R). LEP-R distribution facilitates leptin’s pleiotropic effects, playing a crucial role in regulating body mass via a negative feedback mechanism between adipose tissue and the hypothalamus. Leptin resistance is characterized by reduced satiety, over-consumption of nutrients, and increased total body mass. Often this leads to obesity, which reduces the effectiveness of using exogenous leptin as a therapeutic agent. Thus, combining leptin therapies with leptin sensitizers may help overcome such resistance and, consequently, obesity. This review examines recent data obtained from human and animal studies related to leptin, its role in obesity, and its usefulness in obesity treatment.",
journal = "Frontiers in Endocrinology",
title = "Leptin and Obesity: Role and Clinical Implication",
volume = "12",
pages = "563",
doi = "10.3389/fendo.2021.585887"
}
Obradović, M., Sudar-Milovanović, E., Soskić, S. S., Essack, M., Arya, S., Stewart, A. J., Gojobori, T.,& Isenović, E. R.. (2021). Leptin and Obesity: Role and Clinical Implication. in Frontiers in Endocrinology, 12, 563.
https://doi.org/10.3389/fendo.2021.585887
Obradović M, Sudar-Milovanović E, Soskić SS, Essack M, Arya S, Stewart AJ, Gojobori T, Isenović ER. Leptin and Obesity: Role and Clinical Implication. in Frontiers in Endocrinology. 2021;12:563.
doi:10.3389/fendo.2021.585887 .
Obradović, Milan, Sudar-Milovanović, Emina, Soskić, Sanja S., Essack, Magbubah, Arya, Swati, Stewart, Alan J., Gojobori, Takashi, Isenović, Esma R., "Leptin and Obesity: Role and Clinical Implication" in Frontiers in Endocrinology, 12 (2021):563,
https://doi.org/10.3389/fendo.2021.585887 . .
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401
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306

Suppression of image frequency mode in microprocessor-controlled frequency synthesising systems

Milutinović, N.; Obradović, Milan; Aranđelović, Vojislav; Rodić, R.

(1996)

TY  - JOUR
AU  - Milutinović, N.
AU  - Obradović, Milan
AU  - Aranđelović, Vojislav
AU  - Rodić, R.
PY  - 1996
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1992
AB  - A simple method of starting a new acquisition cycle in microprocessor-controlled frequency synthesising systems in order to suppress the image frequency mode is described. The image frequency detector built into the 305-415 kHz first local oscillator - frequency synthesiser of a 20 Hz - 110 kHz selective voltmeter, supported by an Intel 80C39 microcontroller, identifies the appearance of the image frequency mode in the system and generates a signal to start the procedure carried out by the microcontroller. The microcontroller changes the reference frequency to suppress the signal at the variable input of the phase detector of the phase locked loop (PLL) containing a frequency mixer. This, in turn, forces the phase detector of this PLL to generate an increased voltage, up to 12V, across the associated varactor diode and, by increasing the loop frequency, restore proper functioning of the synthesiser.
T2  - IEE Proceedings: Circuits Devices and Systems
T1  - Suppression of image frequency mode in microprocessor-controlled frequency synthesising systems
VL  - 143
IS  - 3
SP  - 171
EP  - 173
DO  - 10.1049/ip-cds:19960455
ER  - 
@article{
author = "Milutinović, N. and Obradović, Milan and Aranđelović, Vojislav and Rodić, R.",
year = "1996",
abstract = "A simple method of starting a new acquisition cycle in microprocessor-controlled frequency synthesising systems in order to suppress the image frequency mode is described. The image frequency detector built into the 305-415 kHz first local oscillator - frequency synthesiser of a 20 Hz - 110 kHz selective voltmeter, supported by an Intel 80C39 microcontroller, identifies the appearance of the image frequency mode in the system and generates a signal to start the procedure carried out by the microcontroller. The microcontroller changes the reference frequency to suppress the signal at the variable input of the phase detector of the phase locked loop (PLL) containing a frequency mixer. This, in turn, forces the phase detector of this PLL to generate an increased voltage, up to 12V, across the associated varactor diode and, by increasing the loop frequency, restore proper functioning of the synthesiser.",
journal = "IEE Proceedings: Circuits Devices and Systems",
title = "Suppression of image frequency mode in microprocessor-controlled frequency synthesising systems",
volume = "143",
number = "3",
pages = "171-173",
doi = "10.1049/ip-cds:19960455"
}
Milutinović, N., Obradović, M., Aranđelović, V.,& Rodić, R.. (1996). Suppression of image frequency mode in microprocessor-controlled frequency synthesising systems. in IEE Proceedings: Circuits Devices and Systems, 143(3), 171-173.
https://doi.org/10.1049/ip-cds:19960455
Milutinović N, Obradović M, Aranđelović V, Rodić R. Suppression of image frequency mode in microprocessor-controlled frequency synthesising systems. in IEE Proceedings: Circuits Devices and Systems. 1996;143(3):171-173.
doi:10.1049/ip-cds:19960455 .
Milutinović, N., Obradović, Milan, Aranđelović, Vojislav, Rodić, R., "Suppression of image frequency mode in microprocessor-controlled frequency synthesising systems" in IEE Proceedings: Circuits Devices and Systems, 143, no. 3 (1996):171-173,
https://doi.org/10.1049/ip-cds:19960455 . .