• Development of insulin resistance in the obese adolescents changes the expression level of CLU, PCOLCE, COL5A1 and TYMP genes in blood cells 
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Development of insulin resistance in the obese adolescents changes the expression level of CLU, PCOLCE, COL5A1 and TYMP genes in blood cells 

SOVREMENNAYA PEDIATRIYA.2015.7(71):127-130; doi 10.15574/SP.2015.71.127 

Development of insulin resistance in the obese adolescents changes the expression level of CLU, PCOLCE, COL5A1 and TYMP genes in blood cells 

Minchenko D. O., Hnatiuk O. S., Tiazhka O. V., Minchenko O. H.

O.O. Bohomolets National Medical University, Kyiv, Ukraine

Palladin Institute of Biochemistry National Academy of Sciences of Ukraine, Kyiv, Ukraine 

Purpose — to study the expression of genes encoded proteins of extracellular matrix (CLU, COL5A1, PCOLCE та TYMP) in blood cells of obese adolescents with normal and impaired insulin sensitivity. 

Patients and methods. For this study were used three groups of adolescent boys with mean age 14 years: normal (control) and obese individuals with normal and impaired insulin sensitivity. RNA was extracted from blood cells and the levels of gene expressions were studied using quantitative real-time polymerase chain reaction. 

Results. It was shown that the expression level of PCOLCE gene is increased in 1.5 fold, but COL5A1 gene — decreased in the blood cells of obese adolescent boys with normal insulin sensitivity as compared to control group. At the same time, the expression level of CLU та TYMP genes significantly does not changed at these experimental conditions. Insulin resistance in obese boys leads to additional down-regulation of COL5A1 gene expression and decreased expression of PCOLCE і TYMP genes in the blood cells as compared to obese patients with normal insulin sensitivity. Moreover, the changes in TIMP2 and THBS1 were more robust as compared to other studied genes. 

Conclusions. It was shown the expression level of polyfunctional proteins of extracellular matrix COL5A1 and PCOLCE, which control cell proliferation and angiogenesis, are significantly deregulated in blood cells in obese adolescents with normal and suppressed insulin sensitivity and that insulin resistance in obesity is associated with changes in the expression level of all studied genes, which can contribute to the development of insulin resistance. 

Key words: obesity, adolescents, insulin resistance, gene expressions, CLU, PCOLCE, COL5A1, TYMP, blood cells. 


1. Тяжка ОВ, Мінченко ДО, Молявко ОС та ін. 2014. Експресія генів ALDOC, TIGAR, ENO1 та ENO2 у крові дітей чоловічої статі з ожирінням, ускладненим резистентністю до інсуліну. Сучасна педіатрія. 6(62): 112—115.

2. Cheon DJ, Tong Y, Sim MS, Dering J et al. 2014. A collagen-remodeling gene signature regulated by TGF-β signaling is associated with metastasis and poor survival in serous ovarian cancer. Clin Cancer Res. 20;3: 711—723.

3. Yamaoka M, Maeda N, Nakamura S et al. 2012. A pilot investigation of visceral fat adiposity and gene expression profile in peripheral blood cells. PLoS One. 7;10: e47377.

4. Yamaoka M, Maeda N, Takayama Y et al. 2014. Adipose hypothermia in obesity and its association with period homolog 1, insulin sensitivity, and inflammation in fat. PLoS One. 9;11: e112813.

5. Huang W, Ramsey KM, Marcheva В, Bass J. 2011. Circadian rhythms, sleep, and metabolism. J Clin Invest. 121;6: 2133—2141.

6. Ozcan U, Cao Q, Yilmaz E et al. 2004. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 306;5695: 457—461.

7. Salza R, Peysselon F, Chautard E et al. 2014. Extended interaction network of procollagen C-proteinase enhancer-1 in the extracellular matrix. Biochem J. 457;1: 137—149.

8. Hwang S, Lee DH, Lee IK et al. 2014. Far-infrared radiation inhibits proliferation, migration, and angiogenesis of human umbilical vein endothelial cells by suppressing secretory clusterin levels. Cancer Lett. 346;1: 74—83.

9. Ando H, Kumazaki М, Motosugi Y et al. 2011. Impairment of peripheral circadian clocks precedes metabolic abnormalities in ob/ob mice. Endocrinology. 152;4: 1347—1354.

10. Zhu Y, Xu L, Fan Y et al. 2013. Interferon-alpha enhances 5'-deoxy-5-fluorouridine-induced apoptosis by ERK-dependant upregulation of thymidine phosphorylase. Biomed Res Int. 132: 132—793.

11. Kovac J, Husse J, Oster H. 2009. A time to fast, a time to feast: the crosstalk between metabolism and the circadian clock. Mol Cells. 282: 75—80.

12. Lee J, Ozcan U. 2014. Unfolded Protein Response Signaling and Metabolic Diseases. J Biol Chem. 289;3: 1203—1211.

13. Mani? SN, Lebeau J, Chevet E. 2014. Cellular mechanisms of endoplasmic reticulum stress signaling in health and disease. 3. Orchestrating the unfolded protein response in oncogenesis: an update. Am J Physiol Cell Physiol. 307;10: 901—907.

14. Bochkov VN, Philippova M, Oskolkova O et al. 2006. Oxidized phospholipids stimulate angiogenesis via induction of VEGF, IL-8, COX-2 and ADAMTS-1 metalloprotease, implicating a novel role for lipid oxidation in progression and destabilization of atherosclerotic lesions. Circ Res. 99;8: 900—908.

15. Minchenko D, Ratushna O, Bashta Y et al. 2013. The expression of TIMP1, TIMP2, VCAN, SPARC, CLEC3B and E2F1 in subcutaneous adipose tissue of obese males and glucose intolerance. CellBio. 2;2: 25—33.