Downregulation of mapk/mak/mrk overlapping kinase 1 in peripheral blood mononuclear cells of pediatric patients with type 1 diabetes mellitus.

Background

Type 1 diabetes mellitus (T1DM) is one of the most common endocrine diseases in children. T-cell autoreactivity 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 pediatric 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 determined 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.

Informations de copyright

2022 Miron Sopić, Ana Ninić, Barbara Ostanek, Dragana Bojanin, Tatjana Milenković, Jelena Munjas, Marija Mihajlović, Jelena Vekić, Janja Marc, Vesna Spasojević-Kalimanovska, published by CEON/CEES.

Déclaration de conflit d'intérêts

Conflict of Interest: The authors stated that they have no conflicts of interest regarding the publication of this article.