scholarly journals Gly972Arg Variant of Insulin Receptor Substrate 1 Gene and Colorectal Cancer Risk in Overweight/Obese Subjects

2016 ◽  
Vol 31 (1) ◽  
pp. 68-72 ◽  
Author(s):  
Touraj Mahmoudi ◽  
Keivan Majidzadeh-A ◽  
Khatoon Karimi ◽  
Hamid Farahani ◽  
Reza Dabiri ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Insulin Receptor ◽  
Case Control Study ◽  
Insulin Receptor Substrate ◽  
Protective Effects ◽  
Insulin Receptor Substrate 1 ◽  
Pcr Rflp ◽  
Obese Subjects ◽  
Control Study

Background Given the major role of obesity and insulin resistance (IR) in colorectal cancer (CRC), we investigated whether genetic variants in ghrelin ( GHRL), resistin ( RETN) and insulin receptor substrate 1 ( IRS1) were associated with CRC risk. Methods This study was conducted as a case-control study, and 750 subjects, including 438 controls and 312 patients with CRC, were enrolled and genotyped using the PCR-RFLP method. Results No significant differences were observed for GHRL (rs696217), RETN (rs3745367) and IRS1 (rs1801278, Gly972Arg or G972R) gene variants between the cases and controls. However, the IRS1 G972R R allele compared with the G allele and the G972R RR+GR genotype compared with the GG genotype appeared to be markers of decreased CRC susceptibility in the overweight/obese subjects (p = 0.024; odds ratio [OR] = 0.42, 95% confidence interval [95% CI], 0.20-0.91; and p = 0.048; OR = 0.42, 95% CI, 0.17-0.99, respectively). Furthermore, the R allele and RR+GR genotype were also associated with decreased risks for obesity in the patients with CRC (p = 0.007; OR = 0.35, 95% CI, 0.15-0.77; and p = 0.015; OR = 0.35, 95% CI, 0.15-0.72, respectively). Conclusions In accordance with previous studies, our findings suggest that the IRS1 G972R R allele and RR+GR genotype have protective effects for CRC in overweight/obese patients and for obesity in patients with CRC. Nevertheless, further studies are required to confirm these findings.

scholarly journals Flavonoid intake from vegetables and fruits is inversely associated with colorectal cancer risk: a case–control study in China

2016 ◽  
Vol 116 (7) ◽  
pp. 1275-1287 ◽  
Author(s):  
Ming Xu ◽  
Yu-Ming Chen ◽  
Jing Huang ◽  
Yu-Jing Fang ◽  
Wu-Qing Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Risk ◽  
Regression Models ◽  
Case Control Study ◽  
Colorectal Cancer Risk ◽  
Protective Effects ◽  
Flavonoid Intake ◽  
Vegetables And Fruits ◽  
Dietary Flavonoids ◽  
Control Study

AbstractFlavonoids may play an important role in the protective effects of vegetables, fruits and tea against colorectal cancer. However, associations between flavonoids and colorectal cancer risk are inconsistent, and a few studies have evaluated the effect of flavonoids from different dietary sources separately. This study aimed to evaluate associations of flavonoids intake from different dietary sources with colorectal cancer risk in a Chinese population. From July 2010 to December 2015, 1632 eligible colorectal cancer cases and 1632 frequency-matched controls (age and sex) completed in-person interviews. A validated FFQ was used to estimate dietary flavonoids intake. Multivariate logistical regression models were used to calculate the OR and 95 % CI of colorectal cancer risk after adjusting for various confounders. No significant association was found between total flavonoids and colorectal cancer risk, with an adjusted OR of 1·06 (95 % CI 0·85, 1·32) comparing the highest with the lowest quartile. Anthocyanidins, flavanones and flavones intakes from total diet were found to be inversely associated with colorectal cancer risk. Compared with the lowest quartile, the adjusted OR for the highest quartile were 0·80 (95 % CI 0·64, 1·00) for anthocyanidins, 0·28 (95 % CI 0·22, 0·36) for flavanones and 0·54 (95 % CI 0·43, 0·67) for flavones. All subclasses of flavonoids from vegetables and fruits were inversely associated with colorectal cancer. However, no significant association was found between tea flavonoids and colorectal cancer risk. These data indicate that specific flavonoids, specifically flavonoids from vegetables and fruits, may be linked with the reduced risk of colorectal cancer.

14-3-3 Facilitates Insulin-Stimulated Intracellular Trafficking of Insulin Receptor Substrate 1

2002 ◽  
Vol 16 (3) ◽  
pp. 552-562 ◽  
Author(s):  
Xiaoqin Xiang ◽  
Mingsheng Yuan ◽  
Ying Song ◽  
Neil Ruderman ◽  
Rong Wen ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Intracellular Trafficking ◽  
High Speed ◽  
Insulin Treatment ◽  
Insulin Receptor Substrate ◽  
Insulin Receptor Substrate 1 ◽  
Integral Role ◽  
Endogenous Proteins

Abstract The appearance of a complex between tyrosine-phosphorylated insulin receptor substrate 1 (IRS-1) and PI3K in a high-speed pellet fraction (HSP) is thought to be a key event in insulin action. Conversely, the disappearance of the IRS-1/PI3K complex from this fraction has been linked to insulin desensitization. The present study examines the role of 14-3-3, a specific phospho-serine binding protein, in mediating the disappearance of IRS-1 from the HSP after insulin treatment. An in vitro pull-down assay using recombinant 14-3-3 revealed that insulin enhances the association of 14-3-3 with IRS-1 in cultured adipocytes and that this is completely inhibited by wortmannin. An association of IRS-1 and 14-3-3 was also observed and was maximal after stimulation by insulin, when endogenous proteins were immunoprecipitated. Epidermal growth factor (EGF), 12-O-tetradecanoylphorbol-13-acetate, and okadaic acid, other agents that cause serine/threonine phosphorylation of IRS-1, also stimulated IRS binding to 14-3-3. The enhancement of IRS-1 binding to 14-3-3 by insulin was accompanied by movement of IRS-1 and the p85 subunit of PI3K from the HSP to the cytosol. In keeping with a key role of 14-3-3 in mediating this redistribution of IRS-1, the complexes of IRS-1 and 14-3-3 were found in the cytosol but not in the HSP of insulin-treated cells. In addition, colocalization of IRS-1 and 14-3-3 was observed in the cytoplasm after insulin treatment by confocal microscopy. Finally, the addition of a phosphorylated 14-3-3 binding peptide to an adipocyte homogenate (to remove 14-3-3 from IRS-1) increased the abundance of IRS-1/PI3K complexes in the HSP and decreased their abundance in the cytosol. These findings strongly suggest that 14-3-3 participates in the intracellular trafficking of IRS-1 by promoting the displacement of serine-phosphorylated IRS-1 from particular structures. They also suggest that 14-3-3 proteins could play an integral role in the process of insulin desensitization.

scholarly journals Role of the Insulin-Like Growth Factor I/Insulin Receptor Substrate 1 Axis in Rad51 Trafficking and DNA Repair by Homologous Recombination

2003 ◽  
Vol 23 (21) ◽  
pp. 7510-7524 ◽  
Author(s):  
Joanna Trojanek ◽  
Thu Ho ◽  
Luis Del Valle ◽  
Michal Nowicki ◽  
Jin Ying Wang ◽  
...  
Keyword(s):  
Dna Repair ◽  
Growth Factor ◽  
Homologous Recombination ◽  
Insulin Receptor ◽  
Insulin Receptor Substrate ◽  
Insulin Like Growth Factor ◽  
Insulin Receptor Substrate 1 ◽  
Factor I ◽  
Igf I

ABSTRACT The receptor for insulin-like growth factor I (IGF-IR) controls normal and pathological growth of cells. DNA repair pathways represent an unexplored target through which the IGF-IR signaling system might support pathological growth leading to cellular transformation. However, this study demonstrates that IGF-I stimulation supports homologous recombination-directed DNA repair (HRR). This effect involves an interaction between Rad51 and the major IGF-IR signaling molecule, insulin receptor substrate 1 (IRS-1). The binding occurs within the cytoplasm, engages the N-terminal domain of IRS-1, and is attenuated by IGF-I-mediated IRS-1 tyrosine phosphorylation. In the absence of IGF-I stimulation, or if mutated IGF-IR fails to phosphorylate IRS-1, localization of Rad51 to the sites of damaged DNA is diminished. These results point to a direct role of IRS-1 in HRR and suggest a novel role for the IGF-IR/IRS-1 axis in supporting the stability of the genome.

scholarly journals Role of Insulin Receptor Substrate-1 and pp60 in the Regulation of Insulin-induced Glucose Transport and GLUT4 Translocation in Primary Adipocytes

1997 ◽  
Vol 272 (41) ◽  
pp. 25839-25844 ◽  
Author(s):  
Yasushi Kaburagi ◽  
Shinobu Satoh ◽  
Hiroyuki Tamemoto ◽  
Ritsuko Yamamoto-Honda ◽  
Kazuyuki Tobe ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Glucose Transport ◽  
Insulin Receptor Substrate ◽  
Glut4 Translocation ◽  
Insulin Receptor Substrate 1
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