Downregulation of MAPK/MAK/MRK overlapping kinase 1 in peripheral blood mononuclear cells of pediatric patients with type 1 diabetes mellitus

Miron Sopić; Ana Ninić; Barbara Ostanek; Dragana Bojanin; Tatjana Milenković; Jelena Munjas; Marija Mihajlović; Jelena Vekić; Janja Marc; Vesna Spasojević-Kalimanovska

doi:10.5937/jomb0-33220

Downregulation of MAPK/MAK/MRK overlapping kinase 1 in peripheral blood mononuclear cells of pediatric patients with type 1 diabetes mellitus

Miron Sopić Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Serbia
Ana Ninić Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Serbia
Barbara Ostanek Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Slovenia
Dragana Bojanin Mother and Child Health Care Institute of Serbia “Dr Vukan Čupić”, Biochemical Laboratory, Belgrade, Serbia
Tatjana Milenković Mother and Child Health Care Institute of Serbia “Dr Vukan Čupić”, Department of Endocrinology, Belgrade, Serbia
Jelena Munjas Department of Medical Biochemistry, Faculty of Pharmacy. University of Belgrade
Marija Mihajlović Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Serbia
Jelena Vekić Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Serbia
Janja Marc Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Slovenia
Vesna Spasojević-Kalimanovska Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Serbia

DOI: https://doi.org/10.5937/jomb0-33220

Keywords: type 1 diabetes mellitus;, Mammalian target of rapamycin, MAPK/MAK/MRK overlapping kinase 1;

Abstract

Background:

Type 1 diabetes mellitus (T1DM) is one of the most common endocrine diseases in children. T-cell autoreactivity toward β-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, BMI, 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). Multivariate 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).

Conclusion:

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.

Published

2021/11/03

Issue

Vol. 41 No. 3 (2022): Journal of Medical Biochemistry

Section

Original paper

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