Effects of xenoestrogens on streptozotocin-induced diabetic mice.
In diabetic mellitus, apoptotic or necrotic deaths of pancreatic β-cells lead to insulin deficiency because plasma insulin is synthesized and released from pancreatic β-cells and involved with blood glucose homeostasis. Since estrogen receptors have been related with glucose metabolis, estrogen-like chemicals (xenoestrogens) including bisphenol A (BPA) and octylphenol (OP) alter the endocrine system, and cause adverse health consequences such as obesity and diabetes. In the current study, levels of plasma glucose were evaluated after administration of BPA and OP using biochemical analysis, and were investigated in insulin and insulin synthesis-related genes in the pancreas and liver of streptozotocin (STZ)-induced insulin-deficient mice. Although the STZ-induced insulin-deficient groups showed an increase in blood glucose compared with control groups, the induced blood glucose level dropped to that of baseline after administration of xenoestrogens. When insulin level and mRNA expression of insulin transcriptional regulators (Pdx1, Mafa, and Neurod1) in pancreatic β-cells were decreased in STZ-induced insulin-deficient groups, they were significantly restored by administration of xenoestrogens. The latter observation is also related to NF-κB activation for anti-apoptosis effects in pancreatic β-cells. In addition, we observed a complementary convergence in regulation of gluconeogenesis for determination of blood glucose levels. Therefore, the current study may be particularly important for assessment of xenoestrogens under condition of diabetic mellitus or metabolic disorder.
Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea. ebjeung@chungbuk.ac.kr.
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Kang
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Yang
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Ahn
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Kang
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EJ
Hong
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Jaung
D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics; D047629:Estrogen Receptor beta / Q000235:genetics; D004967:Estrogens / Q000494:pharmacology*; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D020672:I-kappa B Proteins / Q000235:genetics; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051473:Maf Transcription Factors, Large / Q000235:genetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D015262:Xenobiotics / Q000494:pharmacology; D051020:bcl-X Protein / Q000235:genetics; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D001786:Blood Glucose; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D051557:Hepatocyte Nuclear Factor 4; D018398:Homeodomain Proteins; D020672:I-kappa B Proteins; D007328:Insulin; D007375:Interleukin-1; D051473:Maf Transcription Factors, Large; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D010636:Phenols; D019253:Proto-Oncogene Proteins c-bcl-2; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D015262:Xenobiotics; D051020:bcl-X Protein; C494812:Bcl2l1 protein, mouse; C467200:Foxo1 protein, mouse; C496593:Hnf4a protein, mouse; C485160:Mafa protein, mouse; C000606205:Nfkbia protein, mouse; C474055:octylphenol; C084010:pancreatic and duodenal homeobox 1 protein; C006780:bisphenol A; D000098826:Bisphenol A Compounds