Expression of genes encoding IGF1, IGF2, and IGFBPs in blood of obese adolescents with insulin resistance

Abstract

Objective. The development of obesity and its metabolic complications is associated with dys-regulation of various intrinsic mechanisms, which control basic metabolic processes via changes in the expression of numerous regulatory genes. The main goal of this work was to study the association between the expression of insulin-like growth factors (IGF1 and IGF2) and IGF-binding proteins and insulin resistance in obese adolescents for evaluation of possible contribution of these genes in development of insulin resistance.Methods. The expression of IGF1, IGF2, and IGFBPs mRNA was measured in blood of obese adolescents with normal insulin sensitivity and insulin resistance in comparison with the normal (control) individuals.Results. In the blood of obese adolescents with normal insulin sensitivity the expression of IGFBP4, IGFBP5 and HTRA1 genes was down-regulated, but IGFBP2 and IGFBP7 genes up-regulated as compared to control (normal) group. At the same time, no significant changes in IGF1 and IGF2 gene expressions in this group of obese adolescents were found. Insulin resistance in obese adolescents led to up-regulation of IGF2, IGFBP2, and IGFBP7 gene expressions as well as to down-regulation of the expression of IGF1, IGFBP5 and HTRA1 genes in the blood in comparison with the obese patients, which have normal insulin sensitivity. Furthermore, the level of IGFBP4 gene expression was similar in both groups of obese adolescents.Conclusions. Results of this investigation provide evidence that insulin resistance in obese adolescents is associated with gene specific changes in the expression of IGF1, IGF2, IGFBP2, IGFBP5, IGFBP7, and HTRA1 genes and these changes possibly contribute to the development of glucose intolerance and insulin resistance.

Hypoxic regulation of EDN1, EDNRA, EDNRB, and ECE1 gene expressions in ERN1 knockdown U87 glioma cells

“…Furthermore, hypoxia stimulates human preproendothelin-1 promoter activity in transgenic mice and in microvascular endothelial cells through interaction of transcription factor HIF with specific hypoxia responsible element in EDN1 promoter (Aversa et al 1997;Minchenko and Caro 2000). However, hypoxic regulation of the EDN1 gene expression is associated with protein kinases and functional activity of other transcriptional factors as well as with signaling pathways of endoplasmic reticulum stress (Minchenko and Caro 2000;Stow et al 2011;Minchenko et al 2015bMinchenko et al , 2017Tsymbal et al 2017;Zhang et al 2018).…”

“…The effect of hypoxia on the expression levels of endothelin-1 and its receptors (EDNRA and EDNRB) mRNAs as well as ECE1 and ACTB mRNAs were measured in control U87 glioma cells and cells with a deficiency of ERN1, introduced by dnERN1 and dnrERN1, by quantitative polymerase chain reaction using SYBRGreen Mix (ABgene, Thermo Fisher Scientific, Epsom, Surrey, UK) and qPCR "Rotor-Gene RG-3000" (Corbett Research, Germany) and "QuantStudio 5 Real-Time PCR System" (Applied Biosystems, USA). Thermo Scien tific Verso cDNA Synthesis Kit (Germany) was used for reverse transcription as described previously (Minchenko et al 2019). Polymerase chain reaction was performed in triplicate.…”

“…It is interesting to note that endoplasmic reticulum stress and hypoxia are two very important and complementary tumor growth factors, and ERN1 mediated stress signaling can significantly modify the effects of hypoxia on gene expressions (Minchenko et al 2014(Minchenko et al , 2015a(Minchenko et al ,b, 2016(Minchenko et al , 2017Tsymbal et al 2017). However, the detailed molecular mechanisms of the iteration of hypoxia with ERN1 mediated stress signaling pathway are complex yet and warrant further study.…”

Effect of glucose deprivation on the expression of genes encoding glucocorticoid receptor and some related factors in ERN1-knockdown U87 glioma cells

“…The effect of glucose deprivation on the expression levels of glucocorticoid receptor (NR3C1) and related proteins (NR3C2, ARHGAP35, AHR, NRIP1, NNT, SGK1, and SGK3 mRNAs as well as ACTB mRNA were measured in control U87 glioma cells and cells with a deficiency of ERN1 by quantitative polymerase chain reaction using SYBRGreen Mix (ABgene, Thermo Fisher Scientific, Epsom, Surrey, UK) and qPCR "RotorGene RG-3000" (Corbett Research, Germany) and "QuantStudio 5 Real-Time PCR System" (Applied Biosystems, USA). QuaniTect Reverse Transcription Kit (QIAGEN, Hilden, Germany) and Thermo Scientific Verso cDNA Synthesis Kit was used for reverse transcription as described previously (Minchenko et al 2015(Minchenko et al , 2019. Polymerase chain reaction was performed in triplicate.…”

Circulating microRNA changes in patients with impaired glucose regulation

“…Regarding the associations between Let-7e and PPARG and between miR-144 and IGFBP2 , no previous studies were found showing such links. However, both genes are known to participate in the regulation of glucose and lipid metabolism [ 50 – 53 ] and our results suggest they can be targets of these miRNAs.…”