Context. Insulin receptor substrate-1 (IRS-1) has an important role in insulin signaling and the common Gly971Arg polymorphism is related to type 2 diabetes (T2D). IRS-1 Gly971Arg polymorphism can modify tyrosine phosphorylation at a specific site of IRS-1 and may have a critical role in the development of insulin resistance (IR).Objective. The purpose of this study was to investigate the association between this polymorphism and IR in Iranian patients with newly-diagnosed type 2 diabetes.Design. The study was conducted on 114 individuals with newly-diagnosed T2D and 118 healthy matched controls, aged 20-80 years. Fasting blood glucose and insulin were measured by the enzymatic method and enzyme-linked immunosorbent assay, respectively. Insulin-resistance was calculated by homeostasis model assessment estimatedinsulin resistance (HOMA-IR). The gene polymorphism was examined by polymerase chain reaction-restriction fragment length polymorphism.Results. There are significant differences between IRS1 Gly971Arg polymorphism and studied individuals (P<0.0001). The findings showed that the risk of developing T2D in individuals who had R-alleles was 3.74 folds higher than those without R-alleles. However, IRS1 Gly971Arg polymorphism was not associated with high HOMA-IR, high BMI and familial history of diabetes.Conclusions. Even though there was not a significant relationship between IRS-1 G971R polymorphism with insulin resistance and high BMI, this polymorphism was correlated to newly-diagnosed diabetic patients. Thus, the evaluation of IRS-1 G971R polymorphism may be helpful for predicting T2D new cases.
Background and Objective: Innate lymphoid cells (ILCs) have been shown to play important roles in tumor immunity. We studied the frequency of three subsets of circulating ILCs in mouse models of colorectal cancer (CRC). Methods: Two mouse models of CRC were developed; including a chemically-induced model, via administration of azoxymethane/dextran sulfate sodium (AOM/DSS), and an orthotopic mouse model, using the CT-26 cell line. Based on histopathological examinations, mice were divided into 3 groups of dysplasia group (consists of chemically-induced and orthotopic induced), chemically-induced reparative change group, normal. A sham group was also considered in which mice were screened for stresses that originated from interventions and injections. Flow cytometry analysis was performed to evaluate the frequencies of ILC1, ILC2, and ILC3 in the peripheral blood of all studied mice.Results: The frequency of ILC1 was significantly higher in the chemically-induced reparative change group compared to the sham and dysplasia groups. ILC2s showed higher frequencies in the dysplasia groups than the sham and chemically-induced reparative change groups. In addition, altered composition of ILCs was observed in peripheral blood of dysplastic mice skewing toward ILC3s in the dysplasia groups compared to sham and chemically-induced reparative change groups. Conclusions: A higher frequency of ILC1 in the reparative change group suggests a potentially anti-tumorigenic role. Higher ILC2s might be in favor of differentiation from the reparative change stage to the dysplasia. In addition, it seems likely that ILC3s are participating in the primary stages of CRC development.
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