Purpose: To investigate whether there are interactions between insulin receptor substrate 1 (IRS1) and insulin receptor substrate 2 (IRS2) that are associated with increased insulin resistance during such episodes. Methods: Testing Haplotype EffectS in Association Studies (THESIAS) software was used to investigate allelic and haplotype interactions between the polymorphisms in 156 T2DM patients...

Insulin receptor substrates, including Irs1 and Irs2, integrate insulin and IGF receptor signals with heterologous pathways to coordinate growth and metabolism. Since Irs2 is thought to be especially important in hepatic nutrient homeostasis, we deleted Irs2 [corrected] from hepatocytes of WT mice (called LKO) or genetically insulin-resistant Irs1-/- mice (called LKO::Irs1-/-). Viable LKO::Irs1...

Hepatitis C virus (HCV) is closely associated with insulin resistance (IS), acting primarily by interfering with insulin signaling pathways, increasing cytokine-mediated (tumor necrosis factor α, interleukin 6) inflammatory responses and enhancing oxidative stress. In the insulin signaling pathways, the insulin receptor substrate (IRS) is one of the key regulatory factors. The present study con...

Aflatoxin B1 (AFB1) is a potent carcinogen that can induce hepatocellular carcinoma. AFB1-8,9-exo-epoxide, one of AFB1 metabolites, acts as a mutagen to react with DNA and induce gene mutations, including the tumor suppressor p53. In addition, AFB1 reportedly stimulates IGF receptor activation. Aberrant activation of IGF-I receptor (IGF-IR) signaling is tightly associated with various types of ...

Insulin signaling depends on tyrosine phosphorylation of insulin receptor substrates (IRSs) to mediate downstream effects; however, elevated serine phosphorylation of IRS impairs insulin signaling. Here, we investigated IRS protein expression patterns in dorsal root ganglia (DRG) of mice and whether their signaling was affected by diabetes. Both IRS1 and IRS2 are expressed in DRG; however, IRS2...

Objective(s): Chronic myelogenous leukemia (CML) is a chronic myeloproliferative disorder characterized by the accumulation of myeloid cells with a chromosomal translocation known as the Philadelphia chromosome. In this study, we investigated the roles of miR-570 in CML development. Materials and Methods: Expression of miR-570 in CML samples and cell lines was determined by qRT-PCR. Glucose upt...

Context Hypoglycemia is the most common metabolic problem among small-for-gestational-age (SGA) neonates. However, the pathological mechanism and insulin/ insulin-like growth factor (IGF) signaling axis in neonates remain unknown. Objective To determine the insulin/IGF axis in neonates, we analyzed the messenger RNA (mRNA) expression of insulin/IGF signaling in fetal umbilical cord blood. S...

Amplification of genes at 13q34 has been reported to be associated with tumor proliferation and progression in diverse types of cancers. However, its role in intrahepatic cholangiocarcinoma (iCCA) has yet to be explored. We examined two iCCA cell lines and 86 cases of intrahepatic cholangiocarcinoma to analyze copy number of three target genes, including cullin 4A (CUL4A), insulin receptor subs...

Here, we aimed to study the effect of the forkhead box O1-insulin receptor substrate 2 (FOXO1-IRS2) gene interaction and the FOXO1 and IRS2 genes-environment interaction for the risk of type 2 diabetes mellitus (T2DM) in a Chinese Han population. We genotyped 7 polymorphism sites of FOXO1 gene and IRS2 gene in 780 unrelated Chinese Han people (474 cases of T2DM, 306 cases of healthy control). T...