RESUMO
The development of obesity and its metabolic complications is associated with dysregulation of various intrinsic mechanisms, which control basic metabolic processes via changes in the expression of numerous regulatory genes. We studied the expression of the subset of genes, which responsible for control of cell growth and glucose metabolism, in blood cells of obese boys with normal and impaired insulin sensitivity as well as in normal (control) individuals. It was shown that obesity with normal insulin sensitivity enhances the expression of IRS1, RIPK2, IL13RA2, RSPO1, IQSEC, and CCN2 genes but decreases the expression level IRS2 and DNAJC15 genes in the blood cells as compared to control group. Insulin resistance in obese boys leads to up-regulation of IRS2, RSPO1, and DNAJC15 gene expressions as wells to down-regulation of IRS1 and RIPK2 genes in the blood cells versus obese patients with normal insulin sensitivity. Results of this study provide evidence that obesity affects the expression of the subset of genes related to cell growth and glucose metabolism in blood cells and that insulin resistance in obesity is associated with changes in the expression level of IRS1, IRS2, RIPK2, RSPO1, and DNA JC15 genes, which contribute to the development of insulin resistance and glucose intolerance and possibly reflect some changes in fat tissue.
Assuntos
Células Sanguíneas/metabolismo , Resistência à Insulina , Obesidade/genética , Adolescente , Células Sanguíneas/patologia , Glicemia/metabolismo , Índice de Massa Corporal , Estudos de Casos e Controles , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Regulação da Expressão Gênica , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Proteínas de Choque Térmico HSP40/genética , Proteínas de Choque Térmico HSP40/metabolismo , Humanos , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Subunidade alfa2 de Receptor de Interleucina-13/genética , Subunidade alfa2 de Receptor de Interleucina-13/metabolismo , Masculino , Obesidade/metabolismo , Obesidade/patologia , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/genética , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/metabolismo , Transdução de Sinais , Trombospondinas/genética , Trombospondinas/metabolismoRESUMO
We studied the expression of genes, which responsible for glucose metabolism, in the blood of obese boys with and without of insulin resistance as well as in normal (control) individuals. It was shown that the expression level of PFKFB3 gene is increased, PFKFB1 and INSIG2--is decreased, but HK2 gene--significantly does not change in the blood cells of obese boys with normal insulin sensitivity as compared to control group. Insulin resistance in obese boys leads to up-regulation of INSIG2 gene expression as well as to down-regulation of PFKFB1, PFKFB3, and HK2 genes in the blood.cells as compared to obese patients with normal insulin sensitivity. Results of this study provide evidence that obesity affects the expression of the subset of glucose metabolism-related genes in the blood cells and that insulin resistance in obesity is associated with changes in the expression level of PFKFB1, PFKFB3, HK2, and INSIG2 genes, which contribute to the development of insulin resistance as well as glucose intolerance.
Assuntos
Células Sanguíneas/metabolismo , Hexoquinase/genética , Resistência à Insulina/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/genética , Obesidade/genética , Fosfofrutoquinase-2/genética , Adolescente , Células Sanguíneas/patologia , Glicemia/metabolismo , Estudos de Casos e Controles , Regulação da Expressão Gênica , Teste de Tolerância a Glucose , Hexoquinase/sangue , Humanos , Insulina/sangue , Insulina/genética , Peptídeos e Proteínas de Sinalização Intracelular/sangue , Isoenzimas/sangue , Isoenzimas/genética , Masculino , Proteínas de Membrana/sangue , Obesidade/sangue , Obesidade/patologia , Fosfofrutoquinase-2/sangue , Transdução de SinaisRESUMO
Endoplasmic reticulum stress and hypoxia are necessary components of malignant tumors growth and suppression of ERN1 (from endoplasmic reticulum to nuclei-1) signalling pathway, which is linked to the apoptosis and cell death processes, significantly decreases proliferative processes. Glioma cells with ERN1 knockdown were used in order to investigate the effect of ERNI blockade on the expression of TP53, MDM2, PERP, and USP7 genes and its hypoxic regulation. We have studied the expression of TP53 (tumor protein 53), MDM2 (TP53 E3 ubiquitin protein ligase homolog), PERP (TP53 apoptosis effector), and USP7 (ubiquitin specific peptidase 7) genes, which are related to cell proliferation and apoptosis, in glioma cells with ERN1 knockdown under hypoxic condition. It was shown that blockade of ERNI gene function in U87 glioma cells intensified the expression of TP53 and USP7 genes, but decreased the expression ofMDM2 and PERP genes. Thus, an enhanced expression of TP53 gene in ERN1 knockdown glioma cells correlates with the decreased level of ubiquitin ligase MDM2 and increased expression level of USP7 which deubiquitinates TP53 and MDM2 and induces TP53-dependent cell growth repression and apoptosis. At the same time, the expression levels of TP53, MDM2, and USP7 genes do not change significantly in glioma cells with suppression of endoribonuclease activity only, but PERP gene expression is strongly increased. Moreover, the expression of TP53 and UPS7 genes is decreased in hypoxic conditions in control glioma cells only; however, MDM2 and PERP gene expressions are increased in both cell types, being more significant in ERN1 knockdown cells. Thus, the expression of genes encoding TP53 and related to TP53 factors depends upon the endoplasmic reticulum stress signaling as well as on hypoxia, and correlates with suppression of glioma growth under ERN1 knockdown.