TY  - JOUR
AU  - Sopić, Miron
AU  - Ninić, Ana
AU  - Ostanek, Barbara
AU  - Bojanin, Dragana
AU  - Milenković, Tatjana
AU  - Munjas, Jelena
AU  - Mihajlović, Marija
AU  - Vekić, Jelena
AU  - Marc, Janja
AU  - Spasojević-Kalimanovska, Vesna
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4255
AB  - Background: Type 1 diabetes mellitus (T1DM) is one of the
most common endocrine diseases in children. T-cell autore-
activity toward b-cells is controlled by significant changes in
metabolism of T cells. Mammalian target of rapamycin
(mTOR) is an important intracellular regulator of metabolism
and cell growth. MAPK/MAK/MRK overlapping kinase 1
(MOK1) is one of the less known regulators of mTOR. We
sought to investigate if MOK1 and mTOR mRNA levels in
peripheral blood mononuclear cells (PBMCs) of T1DM pedi-
atric patients are different compared to healthy subjects.
Methods: This study included 172 adolescents with T1DM
and 36 healthy adolescent volunteers designated for control
group (CG). MOK1 and mTOR mRNA levels were deter-
mined in PBMCs by qPCR.
Results: T1DM patients have significant downregulation of
MOK1 mRNA levels in PBMCs compared CG (P=0.018),
while there was no significant difference in mTOR mRNA
levels (P=0.891). Furthermore, in T1DM patients, MOK1
significantly correlated with age, triglycerides and mTOR,
while mTOR correlated significantly with BMI and systolic
blood pressure. Overweight T1DM subjects had significantly
lower MOK1 (P=0.034) and mTOR (P=0.017) mRNA
levels, together with significantly higher levels of systolic
blood pressure (P<0.001), total cholesterol (P=0.001),
LDL-cholesterol (P=0.001) and CRP (P<0.001). Multi-
variate analysis showed that MOK1 was independently
negatively associated with T1DM when adjusted for sex, age, HDL-C and CRP (OR=0.417 (95%CI: 0.175–0.997),
p=0.049).
Conclusions: Our study demonstrated for the first time that
T1DM is associated with MOK1 downregulation. In addition,
downregulation of both mTOR and MOK1 gene expressions
was associated with cardiovascular risk factors in overweight
T1DM patients.
AB  - Uvod: Dijabetes melitus tip 1 (T1DM) jedno je od najčešćih endokrinih oboljenja kod dece. Autoreaktivnost T-ćelija prema b-ćelijama kontroliše se značajnim promenama u metabolizmu T ćelija. Cilj delovanja rapamicina kod sisara je važan unutarćelijski regulator metabolizma i rasta ćelija. MAPK/MAK/MRK preklapajuće kinaze koja se preklapa (MOK1) jedan je od manje poznatih regulatora mTOR-a. Cilj istraživanja je bio da se ispita da li su nivoi iRNK MOK1 i mTOR u mononuklearnim ćelijama periferne krvi različiti kod pedijatrijskih pacijenata sa T1DM u odnosu na zdrave ispitanike. Metode: Ovo istraživanje je obuhvatilo 172 adolescenta sa T1DM i 36 zdravih adolescenata dobrovoljaca koji su činili kontrolnu grupu (CG). Nivoi MOK1 i mTOR mRNA određeni su u PBMC-ima pomoću qPCR-a. Rezultati: Pacijenti sa T1DM imali su značajno niže nivoe iRNK MOK1 u PBMC u odnosu na CG, dok razlike u nivoima iRNK mTOR nisu bile značajne (P = 0,891). Štaviše, kod pacijenata sa T1DM, MOK1 je značajno korelirao sa godinama, trigliceri dima i mTOR, dok je mTOR značajno korelirao sa BMI i sistolnim krvnim pritiskom. Ispitanici sa prekomernom težinom T1DM imali su značajno niže nivoe iRNK MOK1 (P = 0,034) i mTOR (P = 0,017), zajedno sa značajno većim nivoima sistolnog krvnog pritiska (P <0,001), ukupnog holesterola (P = 0,001), LDL-holesterola (P = 0,001) i CRP (P <0,001). Multivarijantna analiza je pokazala da je MOK1 nezavisno negativno povezan sa T1DM kada je prilagođen polu, starosti, HDL-C i CRP (OR = 0,417 (95%CI: 0,175-0,997), p = 0,049). Zaključak: Naša studija je prva koja je pokazala da je T1DM udružen sa nishodnom regulacijom MOK1. Pored toga, snižena regulacija ekspresije gena mTOR i MOK1 bila je povezana sa kardiovaskularnim faktorima rizika kod pacije nata sa T1DM sa prekomernom težinom.
PB  - Beograd : Društvo medicinskih biohemičara Srbije
T2  - Journal of Medical Biochemistry
T1  - Downregulation of MAPK/MAK/MRK overlapping kinase 1 in peripheral blood mononuclear cells of pediatric patients with type 1 diabetes mellitus
T1  - Nishodna regulacija MAPK/MAK/MRK preklapajuće kinaze u mononuklearnim ćelijama periferne krvi pedijatrijskih pacijenata sa tip1 diiabetes mellitus-om
VL  - 41
IS  - 3
SP  - 282
EP  - 289
DO  - 10.5937/jomb0-33220
ER  - 

@article{
author = "Sopić, Miron and Ninić, Ana and Ostanek, Barbara and Bojanin, Dragana and Milenković, Tatjana and Munjas, Jelena and Mihajlović, Marija and Vekić, Jelena and Marc, Janja and Spasojević-Kalimanovska, Vesna",
year = "2022",
abstract = "Background: Type 1 diabetes mellitus (T1DM) is one of the
most common endocrine diseases in children. T-cell autore-
activity toward b-cells is controlled by significant changes in
metabolism of T cells. Mammalian target of rapamycin
(mTOR) is an important intracellular regulator of metabolism
and cell growth. MAPK/MAK/MRK overlapping kinase 1
(MOK1) is one of the less known regulators of mTOR. We
sought to investigate if MOK1 and mTOR mRNA levels in
peripheral blood mononuclear cells (PBMCs) of T1DM pedi-
atric patients are different compared to healthy subjects.
Methods: This study included 172 adolescents with T1DM
and 36 healthy adolescent volunteers designated for control
group (CG). MOK1 and mTOR mRNA levels were deter-
mined in PBMCs by qPCR.
Results: T1DM patients have significant downregulation of
MOK1 mRNA levels in PBMCs compared CG (P=0.018),
while there was no significant difference in mTOR mRNA
levels (P=0.891). Furthermore, in T1DM patients, MOK1
significantly correlated with age, triglycerides and mTOR,
while mTOR correlated significantly with BMI and systolic
blood pressure. Overweight T1DM subjects had significantly
lower MOK1 (P=0.034) and mTOR (P=0.017) mRNA
levels, together with significantly higher levels of systolic
blood pressure (P<0.001), total cholesterol (P=0.001),
LDL-cholesterol (P=0.001) and CRP (P<0.001). Multi-
variate analysis showed that MOK1 was independently
negatively associated with T1DM when adjusted for sex, age, HDL-C and CRP (OR=0.417 (95%CI: 0.175–0.997),
p=0.049).
Conclusions: Our study demonstrated for the first time that
T1DM is associated with MOK1 downregulation. In addition,
downregulation of both mTOR and MOK1 gene expressions
was associated with cardiovascular risk factors in overweight
T1DM patients., Uvod: Dijabetes melitus tip 1 (T1DM) jedno je od najčešćih endokrinih oboljenja kod dece. Autoreaktivnost T-ćelija prema b-ćelijama kontroliše se značajnim promenama u metabolizmu T ćelija. Cilj delovanja rapamicina kod sisara je važan unutarćelijski regulator metabolizma i rasta ćelija. MAPK/MAK/MRK preklapajuće kinaze koja se preklapa (MOK1) jedan je od manje poznatih regulatora mTOR-a. Cilj istraživanja je bio da se ispita da li su nivoi iRNK MOK1 i mTOR u mononuklearnim ćelijama periferne krvi različiti kod pedijatrijskih pacijenata sa T1DM u odnosu na zdrave ispitanike. Metode: Ovo istraživanje je obuhvatilo 172 adolescenta sa T1DM i 36 zdravih adolescenata dobrovoljaca koji su činili kontrolnu grupu (CG). Nivoi MOK1 i mTOR mRNA određeni su u PBMC-ima pomoću qPCR-a. Rezultati: Pacijenti sa T1DM imali su značajno niže nivoe iRNK MOK1 u PBMC u odnosu na CG, dok razlike u nivoima iRNK mTOR nisu bile značajne (P = 0,891). Štaviše, kod pacijenata sa T1DM, MOK1 je značajno korelirao sa godinama, trigliceri dima i mTOR, dok je mTOR značajno korelirao sa BMI i sistolnim krvnim pritiskom. Ispitanici sa prekomernom težinom T1DM imali su značajno niže nivoe iRNK MOK1 (P = 0,034) i mTOR (P = 0,017), zajedno sa značajno većim nivoima sistolnog krvnog pritiska (P <0,001), ukupnog holesterola (P = 0,001), LDL-holesterola (P = 0,001) i CRP (P <0,001). Multivarijantna analiza je pokazala da je MOK1 nezavisno negativno povezan sa T1DM kada je prilagođen polu, starosti, HDL-C i CRP (OR = 0,417 (95%CI: 0,175-0,997), p = 0,049). Zaključak: Naša studija je prva koja je pokazala da je T1DM udružen sa nishodnom regulacijom MOK1. Pored toga, snižena regulacija ekspresije gena mTOR i MOK1 bila je povezana sa kardiovaskularnim faktorima rizika kod pacije nata sa T1DM sa prekomernom težinom.",
publisher = "Beograd : Društvo medicinskih biohemičara Srbije",
journal = "Journal of Medical Biochemistry",
title = "Downregulation of MAPK/MAK/MRK overlapping kinase 1 in peripheral blood mononuclear cells of pediatric patients with type 1 diabetes mellitus, Nishodna regulacija MAPK/MAK/MRK preklapajuće kinaze u mononuklearnim ćelijama periferne krvi pedijatrijskih pacijenata sa tip1 diiabetes mellitus-om",
volume = "41",
number = "3",
pages = "282-289",
doi = "10.5937/jomb0-33220"
}

Sopić, M., Ninić, A., Ostanek, B., Bojanin, D., Milenković, T., Munjas, J., Mihajlović, M., Vekić, J., Marc, J.,& Spasojević-Kalimanovska, V.. (2022). Downregulation of MAPK/MAK/MRK overlapping kinase 1 in peripheral blood mononuclear cells of pediatric patients with type 1 diabetes mellitus. in Journal of Medical Biochemistry
Beograd : Društvo medicinskih biohemičara Srbije., 41(3), 282-289.
https://doi.org/10.5937/jomb0-33220

Sopić M, Ninić A, Ostanek B, Bojanin D, Milenković T, Munjas J, Mihajlović M, Vekić J, Marc J, Spasojević-Kalimanovska V. Downregulation of MAPK/MAK/MRK overlapping kinase 1 in peripheral blood mononuclear cells of pediatric patients with type 1 diabetes mellitus. in Journal of Medical Biochemistry. 2022;41(3):282-289.
doi:10.5937/jomb0-33220 .

Sopić, Miron, Ninić, Ana, Ostanek, Barbara, Bojanin, Dragana, Milenković, Tatjana, Munjas, Jelena, Mihajlović, Marija, Vekić, Jelena, Marc, Janja, Spasojević-Kalimanovska, Vesna, "Downregulation of MAPK/MAK/MRK overlapping kinase 1 in peripheral blood mononuclear cells of pediatric patients with type 1 diabetes mellitus" in Journal of Medical Biochemistry, 41, no. 3 (2022):282-289,
https://doi.org/10.5937/jomb0-33220 . .