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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 cel...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Society of Medical Biochemists of Serbia, Belgrade
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9375534/ https://www.ncbi.nlm.nih.gov/pubmed/36042901 http://dx.doi.org/10.5937/jomb0-33220 |
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author | Sopić, Miron Ninić, Ana Ostanek, Barbara Bojanin, Dragana Milenković, Tatjana Munjas, Jelena Mihajlović, Marija Vekić, Jelena Marc, Janja Spasojević-Kalimanovska, Vesna |
author_facet | Sopić, Miron Ninić, Ana Ostanek, Barbara Bojanin, Dragana Milenković, Tatjana Munjas, Jelena Mihajlović, Marija Vekić, Jelena Marc, Janja Spasojević-Kalimanovska, Vesna |
author_sort | Sopić, Miron |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9375534 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Society of Medical Biochemists of Serbia, Belgrade |
record_format | MEDLINE/PubMed |
spelling | pubmed-93755342022-08-29 Downregulation of mapk/mak/mrk overlapping kinase 1 in peripheral blood mononuclear cells of pediatric patients with type 1 diabetes mellitus Sopić, Miron Ninić, Ana Ostanek, Barbara Bojanin, Dragana Milenković, Tatjana Munjas, Jelena Mihajlović, Marija Vekić, Jelena Marc, Janja Spasojević-Kalimanovska, Vesna J Med Biochem Original Paper 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. Society of Medical Biochemists of Serbia, Belgrade 2022-07-29 2022-07-29 /pmc/articles/PMC9375534/ /pubmed/36042901 http://dx.doi.org/10.5937/jomb0-33220 Text en 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 https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 License. |
spellingShingle | Original Paper 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 |
title | Downregulation of mapk/mak/mrk overlapping kinase 1 in peripheral blood mononuclear cells of pediatric patients with type 1 diabetes mellitus |
title_full | Downregulation of mapk/mak/mrk overlapping kinase 1 in peripheral blood mononuclear cells of pediatric patients with type 1 diabetes mellitus |
title_fullStr | Downregulation of mapk/mak/mrk overlapping kinase 1 in peripheral blood mononuclear cells of pediatric patients with type 1 diabetes mellitus |
title_full_unstemmed | Downregulation of mapk/mak/mrk overlapping kinase 1 in peripheral blood mononuclear cells of pediatric patients with type 1 diabetes mellitus |
title_short | Downregulation of mapk/mak/mrk overlapping kinase 1 in peripheral blood mononuclear cells of pediatric patients with type 1 diabetes mellitus |
title_sort | downregulation of mapk/mak/mrk overlapping kinase 1 in peripheral blood mononuclear cells of pediatric patients with type 1 diabetes mellitus |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9375534/ https://www.ncbi.nlm.nih.gov/pubmed/36042901 http://dx.doi.org/10.5937/jomb0-33220 |
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