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...
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| Format: | Article |
| Language: | English |
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Society of Medical Biochemists of Serbia, Belgrade
2022-01-01
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| Series: | Journal of Medical Biochemistry |
| Subjects: | |
| Online Access: | https://scindeks-clanci.ceon.rs/data/pdf/1452-8258/2022/1452-82582203282S.pdf |
| _version_ | 1818514265281134592 |
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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 | DOAJ |
| 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. |
| first_indexed | 2024-12-11T00:13:22Z |
| format | Article |
| id | doaj.art-356ff547d5534d93af694e2bb7114121 |
| institution | Directory Open Access Journal |
| issn | 1452-8258 1452-8266 |
| language | English |
| last_indexed | 2024-12-11T00:13:22Z |
| publishDate | 2022-01-01 |
| publisher | Society of Medical Biochemists of Serbia, Belgrade |
| record_format | Article |
| series | Journal of Medical Biochemistry |
| spelling | doaj.art-356ff547d5534d93af694e2bb71141212022-12-22T01:28:04ZengSociety of Medical Biochemists of Serbia, BelgradeJournal of Medical Biochemistry1452-82581452-82662022-01-0141328228910.5937/jomb0-332201452-82582203282SDownregulation of MAPK/MAK/MRK overlapping kinase 1 in peripheral blood mononuclear cells of pediatric patients with type 1 diabetes mellitusSopić Miron0https://orcid.org/0000-0003-3283-9487Ninić Ana1https://orcid.org/0000-0003-3838-1606Ostanek Barbara2Bojanin Dragana3Milenković Tatjana4Munjas Jelena5https://orcid.org/0000-0002-4576-1722Mihajlović Marija6https://orcid.org/0000-0003-3307-0809Vekić Jelena7https://orcid.org/0000-0001-7445-0504Marc Janja8Spasojević-Kalimanovska Vesna9https://orcid.org/0000-0003-1617-7559University of Belgrade, Faculty of Pharmacy, Department of Medical Biochemistry, SerbiaUniversity of Belgrade, Faculty of Pharmacy, Department of Medical Biochemistry, SerbiaUniversity of Ljubljana, Faculty of Pharmacy, Department of clinical Biochemistry, SloveniaMother and Child Health Care Institute of Serbia "Dr Vukan Čupić", Biochemical Laboratory, Belgrade, SerbiaMother and Child Health Care Institute of Serbia "Dr Vukan Čupić", Department of Endocrinology, Belgrade, SerbiaUniversity of Belgrade, Faculty of Pharmacy, Department of Medical Biochemistry, SerbiaUniversity of Belgrade, Faculty of Pharmacy, Department of Medical Biochemistry, SerbiaUniversity of Belgrade, Faculty of Pharmacy, Department of Medical Biochemistry, SerbiaUniversity of Ljubljana, Faculty of Pharmacy, Department of clinical Biochemistry, SloveniaUniversity of Belgrade, Faculty of Pharmacy, Department of Medical Biochemistry, SerbiaBackground: 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.https://scindeks-clanci.ceon.rs/data/pdf/1452-8258/2022/1452-82582203282S.pdftype 1 diabetes mellitusmammalian target of rapamycinmapk/mak/mrk overlapping kinase 1 |
| spellingShingle | 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 Journal of Medical Biochemistry type 1 diabetes mellitus mammalian target of rapamycin mapk/mak/mrk overlapping kinase 1 |
| 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 | type 1 diabetes mellitus mammalian target of rapamycin mapk/mak/mrk overlapping kinase 1 |
| url | https://scindeks-clanci.ceon.rs/data/pdf/1452-8258/2022/1452-82582203282S.pdf |
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