The expression of CСN2, IQSEC, RSPO1, DNAJC15, RIPK2, IL13RA2, IRS1, and IRS2 genes in blood of obese boys with insulin resistance

Abstract

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 well as 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 DNAJC15 genes, which contribute to the development of insulin resistance and glucose intolerance and possibly reflect some changes in fat tissue.

Serum Levels of Interleukin-13 Increase in Subjects with Insulin Resistance but Do Not Correlate with Markers of Low-Grade Systemic Inflammation

“…Then, it is reasonable to speculate that IL-13 plays a protective role in insulin resistance by promoting IRS-1 and AKT phosphorylation in insulin-dependent tissues via STAT3 and STAT6 activation as well as improvement of the beta-cell function. However, together with other studies [ 17 , 24 , 25 ], our work shows a significant increase in the serum levels of IL-13 in insulin-resistant patients, which appears to disagree with previous evidence. In this sense, a previous work showed that IL-13 serum levels significantly increase as the severity of T2D-related chronic heart failure also increases [ 27 ].…”

“…On the contrary, it has been also reported that morbidly obese patients with insulin resistance exhibit higher values of serum IL-13 than normal weight controls, and bariatric surgery was able to reduce IL-13 serum concentrations after 1-year of the surgical procedure [ 24 ]. Likewise, expression of interleukin-13 receptor subunit alpha-2 (IL-13RA2) has been demonstrated to increase in peripheral blood mononuclear cells (PBMC) of obese children with abnormal insulin sensitivity as compared to normal weight boys [ 25 ]. This apparent contradiction could be attributed to the possible role of IL-13 in the insulin resistance pathogenesis that involves the liver, adipose tissue, skeletal muscle, and pancreatic beta-cells.…”

Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons (Review-Hypothesis)

“…Reduced levels of IRS2 in humans have been proposed to lead to desensitized insulin/cytokine signalling and thus to hyperglycemia/muted immune responses, with prolonged IRS2 deficits exacerbating islet cell mass reduction leading to T2DM ( 47 – 50 ). Alterations in IRS2 expression have been associated with altered lipid metabolism in obese subjects ( 51 ) and have been correlated with development of insulin nonresponsiveness in obese boys ( 52 ). IRS2 has eight consecutive Asn-codons located 19 codons after the initiator AUG codon.…”

Insulin resistance in obese adolescents and adult men modifies the expression of proliferation related genes

“…RNA isolation. Trisol reagent (Invitrogen, USA) was used for RNA extraction from the blood of healthy adolescents (without obesity) as control and obese individuals with or without insulin resistan ce as described previously [13]. RNA from subcutaneous adipose tissue samples was extracted using RNasy Lipid Tissue Mini Kit (QIAGEN, Germany) according to the manufacturer's protocol.…”

“…At the same time, the blood reflects numerous changes in different organs and tissues in various diseases including obesity [10,11]. Special interest deserves the key regulatory factors, which control cell pro-liferation, glucose and lipid metabolism as well as endoplasmic reticulum stress [2,4,8,12,13]. Thus, adolescent obesity is associated with increased expression of IRS1, ССN2, IGSec, RSPO1, IL13RA2, and RIPK2 genes and down-regulated IRS2 and DNaJc15 gene expressions, although with insulin resistance is associated the expression IRS1, IRS2, DNaJc15, RSPO1, and RIPK2 genes only [13].…”