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Pathophysiology
Investigating Susceptibility to Diabetes Using Features of the Adipose Tissue in Response to In Utero Polycyclic Aromatic Hydrocarbons Exposure
Worlanyo E. Gato, Daniel A. Hunter, Shamaya L. Whitby, Christopher A. Mays, Wilson Yau
Diabetes Metab J. 2016;40(6):494-508.   Published online August 12, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.6.494
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  • 91 Download
  • 7 Web of Science
  • 5 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   
Background

In recent times, there has been an increase in the incidence of type 2 diabetes mellitus (T2DM) particularly in children. Adipocyte dysfunction provide a critical link between obesity and insulin resistance resulting in diabetes outcome. Further, environmental chemical exposure during early years of life might be a significant contributing factor to the increase in the incidence of T2DM. This study tests the idea that exposure to environmental contaminants (2-aminoanthracene [2AA]) in utero will show effects in the adipose tissue (AT) that signify T2DM vulnerability. 2AA is a polycyclic aromatic hydrocarbon found in a variety of products.

Methods

To accomplish the study objective, pregnant dams were fed various amounts of 2AA adulterated diets from gestation through postnatal period. The neonates and older offspring were analyzed for diabetic-like genes in the ATs and analysis of serum glucose. Furthermore, weight monitoring, histopathology and immunohistochemical (IHC) staining for CD68 in AT, adipocyte size determination and adiponectin amounts in serum were undertaken.

Results

Up-regulation of adiponectin and interleukin-6 genes were noted in the pups and older rats. Combination of intrauterine 2AA toxicity with moderate high fat diet exhibited gene expression patterns similar to those of the neonates. Elevated serum glucose levels were noted in treated groups. IHC of the AT indicated no significant malformations; however, CD68+ cells were greater in the animals treated to 2AA. Similarly, mean sizes of the adipocytes were larger in treated and combined 2AA and moderate high fat animals. Adiponectin was reduced in 2AA groups.

Conclusion

From the preceding, it appears intrauterine 2AA disturbance, when combined with excess fat accumulation will lead to greater risk for the diabetic condition.

Citations

Citations to this article as recorded by  
  • The Role of Persistent Organic Pollutants in Obesity: A Review of Laboratory and Epidemiological Studies
    Jan Aaseth, Dragana Javorac, Aleksandra Djordjevic, Zorica Bulat, Anatoly Skalny, Irina Zaitseva, Michael Aschner, Alexey Tinkov
    Toxics.2022; 10(2): 65.     CrossRef
  • The Association between Urinary Polycyclic Aromatic Hydrocarbons Metabolites and Type 2 Diabetes Mellitus
    Xue Wang, Ang Li, Qun Xu
    International Journal of Environmental Research and Public Health.2022; 19(13): 7605.     CrossRef
  • Dietary ingestion of 2-aminoanthracene (2AA) and the risk for type-1 diabetes (T1D)
    Isaiah Seise, Zachary A. Pilz, Moses Yeboah Kusi, Bethany Bogan, Brittany Jean McHale, Worlanyo E. Gato
    Journal of Environmental Science and Health, Part A.2020; 55(14): 1638.     CrossRef
  • Association of the IL6 Gene Polymorphism with Component Features of Metabolic Syndrome in Obese Subjects
    Elham Barati, Hamideh Ghazizadeh, Fatemeh Sadabadi, Elham Kazemi, Gordon A. Ferns, Amir Avan, Majid Ghayour-Mobarhan
    Biochemical Genetics.2019; 57(5): 695.     CrossRef
  • The hepatic effects in dams that ingested 2-aminoanthracene during gestation and lactation
    Raven E Ulieme, Surjania Awer, John C Stagg, Wilson Yau, Worlanyo E Gato
    Toxicology and Industrial Health.2019; 35(9): 568.     CrossRef
The Association of Interleukin-6 Gene Promoter Region Polymorphism G174C with Insulin Resistance and Metabolic Syndrome in Korean Women.
Eun Jung Rhee, Won Young Lee, Se Yeon Kim, Eun Sook Oh, Ki Hyun Baek, Ki Won Oh, Moo Il Kang, Sun Woo Kim
Korean Diabetes J. 2005;29(3):181-188.   Published online May 1, 2005
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  • 16 Download
AbstractAbstract PDF
BACKGROUND
Interleukin(IL)-6 is a cytokine that is produced from immune cells and adipose tissue. It is thought to be a factor to explain the link between insulin resistance and inflammation, and it is also thought to be involved in glucose metabolism and lipid metabolism. We observed the frequency of the G174C polymorphism in the IL-6 gene promoter region in Korean women and we investigated the association of fasting glucose, insulin resistance indices and metabolic syndrome. METHODS: Measurements of the blood pressure, body fat, fasting glucose, insulin, lipid profiles and anthropometric measurements were done for 268 Korean women(mean age 51.4yrs, range 37~73yrs). Homeostasis model assessement(HOMA) and the quantitative insulin sensitivity check index(QUICKI) were calculated and the presence of metabolic syndrome was assessed according to ATP III criteria. Genotyping was done with the PCRRFLP method on the blood samples of the participants. RESULTS: The allele frequencies were 0.965 for the G allele and 0.035 for the C allele, and they were in Hardy-Weinberg equilibrium(P=0.50). The fasting insulin level and HOMA were significantly higher and the QUICKI was significantly lower in the C allele carriers compared with non-carriers. Although the prevalence of metabolic syndrome was not significantly different according to the different genotypes, among the individual components, the prevalence of hypertriglyceridemia was significantly higher in the C allele carriers compared with the non-carriers. There were no differences in the prevalence of normoglycemia, fasting hyperglycemia and provisional diabetes according to the different genotypes. CONCLUSION: The G174C polymorphism in The IL-6 promoter region was not frequently observed in Korean women. The insulin resistance indices were higher in the C allele carriers compared with the non-carriers. Although the prevalence of metabolic syndrome was not associated with the polymorphism, the prevalence of hypertriglyceridemia was higher in The C allele carriers, suggesting that it is possibile for candidate gene of insulin resistance
Interleukin-6 polymorphism in Korean Obese and Type 2 Diabetic Subjects.
Jae Taek Kim, Seung Jin Choi, Mi Kyung Lee, Ae Ja Park, Yeon Sahng Oh, Soon Hyun Shin
Korean Diabetes J. 2001;25(5):337-342.   Published online October 1, 2001
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  • 16 Download
AbstractAbstract PDF
BACKGROUND
Interleukin (IL)-6 is produced by many different cell types, including adipose tissue, and the release is greater in obese subjects. Recently, it has been reported that polymorphism in the 5' flanking region of the IL-6 gene may contribute to the insulin resistance and lipid abnormality. However, there are limited number of studies reported on the relationship between IL-6 polymorphism and insulin resistance syndrome. Therefore, the aim of this study was to examine the relationships among this polymorphism, obesity and diabetes in Korean subjects. METHODS: We examined a total of 177 Korean individuals, including 113 type 2 diabetic subjects. Sixty-three subjects were non-obese diabetics (age; 56.4+/-9.8 yr, body mass index (BMI); 22.5+/-1.7 kg/m2), 50 of them were obese diabetic subjects (age; 54.8+/-10.7 yr, BMI; 27.6+/-2.2 kg/m2), and 64 were overweight or obese subjects (age; 49.1+/-11.4 yr, BMI; 25.4 1.5 kg/m2). We evaluated IL-6 gene polymorphism using PCR-restriction fragment length polymorphism. RESULTS: There were 176 GG (99.4%), 1 GC (0.56%) and 0 CC (0%) individuals, and the allele frequencies were 99.7% for G and 0.28% for C. Allele frequencies of C in obese diabetic subjects were 1.02%. The frequency of C allele was substantially lower than that reported in Caucasian. CONCLUSION: This results suggest that the IL-6 polymorphism is not associated with obesity nor diabetes in Korean subjects.

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