scholarly journals The Role of Insulin, IGF-1 and PRAS40 in the Processes of Oncogenesis in Women with Type 2 Diabetes Mellitus and Endometrial Cancer

2019 ◽  
Vol 26 (4) ◽  
Author(s):  
Tamara Vatseba
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Type 2 Diabetes Mellitus ◽  
Endometrial Cancer ◽  
Growth Factor ◽  
Group Iv ◽  
Insulin Like Growth Factor ◽  
Group Iii

The objective of the research was to investigate the content of insulin, insulin-like growth factor-1 and phosphorylated protein kinase proline-rich Akt substrate of 40kDa and to determine their role in the activation of oncogenesis processes in women with type 2 diabetes mellitus and endometrial cancer. Materials and methods. There were examined 46 women who were divided into 4 groups: Group I included healthy women; Group II comprised women with type 2 diabetes mellitus; Group III included women with endometrial cancer; Group IV comprised women with endometrial cancer and co-existent type 2 diabetes mellitus. The levels of insulin, insulin-like growth factor-1, phospho- proline-rich Akt substrate of 40kDa were determined by immune-enzyme analysis. The compensation of diabetes mellitus was evaluated by hemoglobin A1c level using method of ion-exchange chromatography. The results obtained were analyzed using statistical analysis. Results. Women of all study groups had increased levels of insulin and insulin-like growth factor-1 as compared to the control group (p<0.05). The level of phospho-proline-rich Akt substrate of 40kDa increased in the patients of Group II (p<0.05) and the patients of Group III (p<0.05) and decreased in the patients of Group IV (p<0.05). According to correlation analysis, phospho-proline-rich Akt substrate of 40kDa was found to correlate with body mass index, insulin and insulin-like growth factor-1 in Group II, body mass index and insulin-like growth factor-1 in Group III and body mass index in Group IV (p<0.05). Conclusions. There was found an association between type 2 diabetes mellitus and endometrial cancer through obesity, hyperinsulinemia and insulin-like growth factor-1. The increase in phospho- proline-rich Akt substrate of 40kDa level was a sign of activation of mTOR and oncogenesis processes in the patients with type 2 diabetes mellitus. The decrease in phospho-proline-rich Akt substrate of 40kDa in the patients with endometrial cancer and co-existent type 2 diabetes mellitus can be explained by the influence of other intracellular regulatory systems or the effects of antidiabetic drugs, that requires additional study.

scholarly journals Association Between Insulin-like Growth Factor-1 rs35767 Polymorphism and Type 2 Diabetes Mellitus Susceptibility: A Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Qiaoli Zeng ◽  
Dehua Zou ◽  
Qiaodi Zeng ◽  
Xiaoming Chen ◽  
Yue Wei ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Growth Factor ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Genetic Models ◽  
Insulin Like Growth Factor ◽  
Allele Model

Background: Insulin-like growth factor-1 (IGF-1) has been demonstrated to increase fatty acid β oxidation during fasting, and play an important role in regulating lipid metabolism and type 2 diabetes mellitus (T2DM). The rs35767 (T &gt; C) polymorphism, a functional SNP was found in IGF-1 promoter, which may directly affect IGF-1 expression. However, the inconsistent findings showed on the IGF-1 rs35767 polymorphism and T2DM risk.Methods: We performed a comprehensive meta-analysis to estimate the association between the IGF-1 rs35767 and T2DM risk among four genetic models (the allele, additive, recessive and dominant models).Results: A total 49,587 T2DM cases and 97,906 NDM controls were included in the allele model, a total 2256 T2DM cases and 2228 NDM controls were included in the other three genetic models (the additive; recessive and dominant models). In overall analysis, the IGF-1 rs35767 was shown to be significantly associated with increased T2DM risk for the allele model (T vs. C: OR = 1.251, 95% CI: 1.082–1.447, p = 0.002), additive model (homozygote comparisons: TT vs. CC: OR = 2.433, 95% CI: 1.095–5.405, p = 0.029; heterozygote comparisons: TC vs. CC: OR = 1.623, 95% CI: 1.055–2.495, p = 0.027) and dominant model (TT + CT vs. CC: OR = 1.934, 95% CI: 1.148–3.257, p = 0.013) with random effects model. After omitting Gouda’s study could reduce the heterogeneity, especially in the recessive model (TT vs. CC + CT: I2 = 38.7%, p = 0.163), the fixed effects model for recessive effect of the T allele (TT vs. CC + CT) produce results that were of borderline statistical significance (OR = 1.206, 95% CI: 1.004–1.448, p = 0.045). And increasing the risk of T2DM in Uyghur population of subgroup for the allele model.Conclusion: The initial analyses that included all studies showed statistically significant associations between the rs35767 SNP and type 2 diabetes, but after removing the Gouda et al. study produced results that were mostly not statistically significant. Therefore, there is not enough evidence from the results of the meta-analysis to indicate that the rs35767 SNP has a statistically significant association with type 2 diabetes.

scholarly journals Insulin receptor substrate-1 G972R single nucleotide polymorphism in Egyptian patients with chronic hepatitis C virus infection and type 2 diabetes mellitus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rania Nabil Bedair ◽  
Gehan M. Magour ◽  
Said Ahmed Ooda ◽  
Eman M. Amar ◽  
Ahmed M. Awad
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Group Iv ◽  
Group Iii ◽  
Egyptian Patients

Abstract Background Insulin receptor substrate-1 (IRS1) plays a critical role in insulin signaling. IRS-1 gene polymorphism with glycine to arginine substitution (GGG ↔ AGG substitutions) in codon 972 (G972R) (rs1801278) is a common polymorphism of the IRS-1 gene, which may have a pathogenic role in the development of type 2 diabetes mellitus (type 2 DM) due to insulin resistance and impaired insulin secretion. In hepatitis C virus infection (HCV), the IRS proteins might be counter-regulated by degradation, differential expression, or modification by phosphorylation in cells expressing HCV core protein, which inhibits the interactions of IRS-1 with both the insulin receptor and the downstream effectors of IRS-1. The present retrospective case–control study aimed to evaluate IRS-1 G972R (rs 1801278) SNP in Egyptian patients with HCV and type 2 DM, two hundred and two subjects including 100 males and 102 females The present work is a retrospective case–control study aimed to detect IRS-1 G972R (rs 1801278) SNP in Egyptian patients with chronic HCV infection and DM. The subjects were divided into the control group (group I) which included 50 apparently healthy volunteers of comparable age, gender, and socioeconomic status to patients; group II included 50 type 2 diabetic patients without chronic hepatitis C infection; group III included 52 chronic HCV-infected patients without type 2 diabetes mellitus; and group IV included 50 chronic hepatitis C-infected patients with type 2 diabetes mellitus. IRS-1 G972R (rs 1801278) genotyping was done by using polymerase chain reaction (PCR-RFLP) technique with restriction enzymes BstNI. Results HOMA-IR and QUICKI index was significantly higher in the patient groups (groups II, III, and IV) than controls (P < 0.001, P = 0.019, and P < 0.001 respectively). There was a significant increase in minor allele (A) in groups II, III, and IV than controls (P = 0.007, P = 0.017, and P = 0.007 respectively). There was increased frequency of mutant allele (A) than wild allele (G) of IRS-1 G972R polymorphism in type 2 diabetic patients with BMI < 25 kg/m2. The DM patients without HCV infection (group II), HCV patients without DM (group III), and HCV patients with DM (group IV) showed a significant decrease in GG genotypes and a significant increase in AA genotypes than the controls (P = 0.017, P = 0.019, and P = 0.009 respectively). Body mass index and waist to hip ratio were significantly higher in DM patients without chronic hepatitis C infection (group II) and in HCV patients with type 2 diabetes (group IV) than controls, in hepatitis C patients with type 2 diabetes (group IV) than controls, and in group IV than group III (P < 0.001). Conclusion IRS-1 G972R (rs 1801278) polymorphism might be a contributing risk factor for the development of type 2 DM. The mutant allele (A) of IRS-1 suggests the role of this SNP as risk factors for type 2 diabetes mellitus even in subjects with normal body weight. The increase of body mass index may be an independent risk factor for the development of type 2 diabetes mellitus.

scholarly journals Insulin‐like growth factor‐1 is inversely associated with liver fibrotic markers in patients with type 2 diabetes mellitus

2019 ◽  
Vol 10 (4) ◽  
pp. 1083-1091 ◽  
Author(s):  
Shozo Miyauchi ◽  
Teruki Miyake ◽  
Masumi Miyazaki ◽  
Toru Eguchi ◽  
Tetsuji Niiya ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Growth Factor ◽  
Insulin Like Growth Factor
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