Ahr and CYP1B1 gene expression in type 2 diabetes patients in Vietnam

Le Hoang Duc; Nguyen Trung Nam

doi:10.15625/1811-4989/15000

Author affiliations

Authors

Le Hoang Duc Institute of Biotechnology, Vietnam Academy of Science and Technology
Nguyen Trung Nam Institute of Biotechnology, Vietnam Academy of Science and Technology

DOI:

https://doi.org/10.15625/1811-4989/15000

Keywords:

Ahr, Cyp1b1, blood glucose level, qPCR, type 2 diabetes

Abstract

Type 2 diabetes is a chronic disease, which has risen dramatically in many countries in the world, including Vietnam. Recently, there is increasing evidence about the link between type 2 diabetes and the exposure to Ahr ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the experimental animal model. In the cell, after activation by the ligands, Ahr moves from the cytoplasm into the nucleus and binds to the nuclear translocator, resulting in transcription of target genes such as Cyp1b1. The development of type 2 diabetes was shown in some people who exposed to TCDD. However, the role of Ahr/Cyp1b1 genes in type 2 diabetes patients has not been elucidated. In this study, the expression of the Ahr and Cyp1b1 genes in blood samples collected from patients with type 2 diabetes and controls was studied for the first time in Vietnam. Analysis of blood glucose showed that this index in the type 2 diabetes patients was higher than that in the control group. Using real-time PCR method, the results showed that the expression of Ahr and Cyp1b1 in type 2 diabetes patients was significantly higher than that in control group. In addition, the expression of Ahr and Cyp1b1 was positively correlated with the blood glucose levels of both groups. These results are initial evidence for the link between activation of Ahr/Cyp1b1 signaling pathway and level of blood glucose so that Ahr/Cyp1b1 genes can be potential targets to treat type 2 diabetes.

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References

Donath MY, Shoelson SE (2011) Type 2 diabetes as an inflammatory disease. Nat Rev Immunol 11: 98–107.

Fujiyoshi PT, Michalek JE, Matsumura F (2006) Molecular epidemiologic

evidence for diabetogenic effects of dioxin exposure in U.S. Air force veterans of

the Vietnam war. Environ Health Perspect 114:1677-1683.

Ibrahim MM, Fjære E, Lock EJ, Naville D, Amlund H, Meugnier E, Le Magueresse Battistoni B, Frøyland L, Madsen L, Jessen N, Lund S, Vidal H, Ruzzin J (2011) Chronic consumption of farmed salmon containing persistent organic pollutants causes insulin resistance and obesity in mice. PLoS One 6:e25170.

Jacob A, Hartz AM, Potin S, Coumoul X, Yousif S, Scherrmann JM, Bauer B, Declèves X (2011) Aryl hydrocarbon receptor-dependent upregulation of Cyp1b1 by TCDD and diesel exhaust particles in rat brain microvessels. Fluids Barriers CNS 8:23.

Kerley-Hamilton JS, Trask HW, Ridley CJ, Dufour E, Ringelberg CS, Nurinova N, Wong D, Moodie KL, Shipman SL, Moore JH, Korc M, Shworak NW, Tomlinson CR (2012) Obesity is mediated by differential aryl hydrocarbon receptor signaling in mice fed a Western diet. Environ Health Perspect 120(9): 1252–1259.

Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2-Ct method. Methods 25(4): 402–408.

Nguyen CH, Nakahama T, Dang TT, Chu HH, Van Hoang L, Kishimoto T, Nguyen NT (2017) Expression of aryl hydrocarbon receptor, inflammatory cytokines, and incidence of rheumatoid arthritis in Vietnamese dioxin-exposed people. J Immunotoxicol 14(1): 196-203.

Nguyen NT, Hanieh H, Nakahama T, Kishimoto T (2013) The roles of aryl hydrocarbon receptor in immune responses. Int Immunol 25(6): 335-343.

Nault R, Kim S, Zacharewski TR (2013) Comparison of TCDD-elicited genomewide hepatic gene expression in Sprague-Dawley rats and C57BL/6 mice. Toxicol Appl Pharmacol 267: 184-191.

Mimura J, Ema M, Sogawa K, Fujii-Kuriyama Y (1999) Identification of a novel mechanism of regulation of Ah (dioxin) receptor function. Genes Dev 13(1): 20-25.

Roh E, Kwak SH, Jung HS, Cho YM, Pak YK, Park KS, Kim SY, Lee HK (2015) Serum aryl hydrocarbon receptor ligand activity is associated with insulin resistance and resulting type 2 diabetes. Acta Diabetol 52(3): 489-495.

Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, Colagiuri S, Guariguata L, Motala AA, Ogurtsova K, Shaw JE, Bright D, Williams R; IDF Diabetes Atlas Committee (2019) Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract 157: 107843.

Ngoc NB, Lin ZL, Ahmed W (2020) Diabetes: What Challenges Lie Ahead for Vietnam? Ann Glob Health. 86(1):1.

Toan NL, Hoan NV, Cuong DV, Dung NV, Dung PT, Hang NT, Dieu DTH, Chung DT, Son HA, Phong PX, Lenon GB, De DV, Tong HV (2018) Adipose tissue-derived cytokines and their correlations with clinical characteristics in Vietnamese patients with type 2 diabetes mellitus. Diabetol Metab Syndr 10: 41.

Wang C, Xu CX, Krager SL, Bottum KM, Liao DF, Tischkau SA (2011) Aryl hydrocarbon receptor deficiency enhances insulin sensitivity and reduces PPAR-α pathway activity in mice. Environ Health Perspect 119(12): 1739-1744.

Yang X, Solomon S, Fraser LR, Trombino AF, Liu D, Sonenshein GE, Hestermann EV, Sherr DH (2008) Constitutive regulation of CYP1B1 by the aryl hydrocarbon receptor (Ahr) in pre-malignant and malignant mammary tissue. J Cell Biochem 104(2): 402-417.

Zhu Z, Mu Y, Qi C, Wang J, Xi G, Guo J, Mi R, Zhao F (2015) CYP1B1 enhances the resistance of epithelial ovarian cancer cells to paclitaxel in vivo and in vitro. Int J Mol Med 35(2):340-348.