Profile of Six Hepatic Insulin Signaling Pathway Genes in Response to 2-Aminoanthracene Dietary Ingestion

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Six genes that regulate various processes in the insulin signaling pathway were profiled. These transcripts were reported to regulate other genes that are essential for glucose metabolism, fatty acid and lipid biosynthesis. In a previous he-patic global gene expression analysis followed by DAVID bioinformatics analytics showed ampk, g6pc, gck, pp1, srebp-1C and socs2 to be likely modulated by 2-aminoanthracene (2AA) dietary consumption. The goal of the current study is to evaluate the responses of these proteins in the liver of Fisher-344 (F344) rats exposed to 2AA. 2AA belongs to a class of compounds referred to as polycyclic aromatic hydrocarbons (PAHs). This compound has been detected in broiled food and tobacco smoke. F344 rats were fed 2AA adulterated diets of 0 mg/kg, 50 mg/kg, 75 mg/kg and 100 mg/kg for 14- and 28-days. Differential gene expression of ampk (Prkab1), g6pc, gck, pp1, srebp-1C, socs2 and gapdh were be carried out by qRT-PCR. Results seem to suggest 2AA modulates different genes related to energy metabolism in the liver. Relative quantification of these products indicated an up-regulation of the ampk and socs in animals treated to 100 mg/kg-diet and 50 mg/kg-diet respectively during 14 days of feeding. The rest of the mRNA transcripts were down-regulated in the treated rats relative to the control group. G6pc gene was highly up-regulated in all animals that ingested 2AA for 28 days. Pp1 protein was also up-regulated in the 75 mg/kg-diet rats. The rest of the genes tested were not differentially altered. This result will be followed by a protein immunoblot assay to examine the expression of g6pc and ampk.


Society of Toxicology Annual Meeting (SOT)


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