Sopić Miron, Ninić Ana, Ostanek Barbara, Bojanin Dragana, Milenković Tatjana, Munjas Jelena, Mihajlović Marija, Vekić Jelena, Marc Janja, Spasojević-Kalimanovska Vesna
University of Belgrade, Faculty of Pharmacy, Department of Medical Biochemistry.
University of Ljubljana, Faculty of Pharmacy, Department of clinical Biochemistry, Slovenia.
J Med Biochem. 2022 Jul 29;41(3):282-289. doi: 10.5937/jomb0-33220.
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.
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.
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).
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.
1型糖尿病（T1DM）是儿童最常见的内分泌疾病之一。T细胞对β细胞的自身反应性受T细胞代谢的显著变化控制。雷帕霉素靶蛋白（mTOR）是细胞内代谢和细胞生长的重要调节因子。丝裂原活化蛋白激酶/微管相关蛋白激酶/丝裂原活化蛋白激酶重叠激酶1（MOK1）是mTOR鲜为人知的调节因子之一。我们试图研究T1DM儿科患者外周血单个核细胞（PBMC）中MOK1和mTOR mRNA水平与健康受试者相比是否存在差异。
本研究纳入172例患有T1DM的青少年和36名健康青少年志愿者作为对照组（CG）。通过qPCR测定PBMC中的MOK1和mTOR mRNA水平。
与CG相比，T1DM患者PBMC中MOK1 mRNA水平显著下调（P = 0.018），而mTOR mRNA水平无显著差异（P = 0.891）。此外，在T1DM患者中，MOK1与年龄、甘油三酯和mTOR显著相关，而mTOR与BMI和收缩压显著相关。超重的T1DM受试者MOK1（P = 0.034）和mTOR（P = 0.017）mRNA水平显著较低，同时收缩压（P < 0.001）、总胆固醇（P = 0.001）、低密度脂蛋白胆固醇（P = 0.001）和CRP（P < 0.001）水平显著较高。多变量分析显示，在调整性别、年龄、高密度脂蛋白胆固醇和CRP后，MOK1与T1DM独立呈负相关（OR = 0.417（95%CI：0.175 - 0.997），p = 0.049）。
我们的研究首次证明T1DM与MOK1下调有关。此外，mTOR和MOK1基因表达的下调与超重T1DM患者的心血管危险因素有关。
