title: Profile of select hepatic insulin signaling pathway genes in response to 2-aminoanthracene dietary ingestion.
abstract: Some genes that regulate various processes such as insulin signaling, glucose metabolism, fatty acid, and lipid biosynthesis were profiled. The objective of the current investigation is to examine the mRNA expression of some genes that mediate insulin signaling due to 2AA toxicity. 2AA is a polycyclic aromatic hydrocarbon (PAH) that has been detected in broiled food and tobacco smoke. Twenty-four post-weaning 3-4-week-old F344 male rats were exposed to 0 mg/kg-diet, 50 mg/kg-diet, 75 mg/kg-diet, and 100 mg/kgdiet 2AA for 2 weeks and 4 weeks. The mRNA expression of AKT1, G6PC, GCK, GLUT4, INSR, IRS1, PP1R3C, PAMPK, SOCS 2, and SREBF1 was determined by qRTPCR followed by the quantification of G6PC and AMPK via ELISA. The results suggest that 2AA modulates these genes depending on the length of exposure. Up-regulation of AMPK and SOCS2 genes in animals treated with 100 mg/kg-diet and 50 mg/kg-diet, respectively, during 14 days of feeding was noted. G6PC expression was inhibited in the 2-week group while being dose-dependently increased in the 4-week group. Hepatic activity of G6PC was enhanced significantly in the livers of rats that ingested 2AA. It appears that 2AA intoxication leads to the activation of irs1 and akt1 genes in the liver. Quantified AMPK amounts increased significantly in the short-term treatment group. Dose-dependent rise of AMPK in animals treated to 2AA showed an increased production of hepatic AMPK in response to the toxicity of 2AA in order to maintain cellular homeostasis. In contrast, the reduction in AMPK concentration in treated animals within the 4-week set indicated an adaptive recovery.
authors.affiliation: Department of Chemistry, Georgia Southern University, Statesboro, GA USA.
authors.forename: N D
authors.initials: ND
authors.lastname: Mattis
authors.affiliation: Department of Chemistry, Georgia Southern University, Statesboro, GA USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Jay
authors.affiliation: Department of Chemistry, Georgia Southern University, Statesboro, GA USA.
authors.forename: G W
authors.initials: GW
authors.lastname: Barnett
authors.affiliation: Department of Chemistry, Georgia Southern University, Statesboro, GA USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Rosaldo
authors.affiliation: Department of Pathology, College of Veterinary Medicine, The University of Georgia, Athens, GA, USA.
authors.forename: E W
authors.initials: EW
authors.lastname: Howerth
authors.affiliation: Bren School of Environmental Science and Management, UC Santa Barbara, Santa Barbara, CA, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Means
authors.affiliation: Department of Chemistry, Georgia Southern University, Statesboro, GA USA.
authors.forename: W E
authors.initials: WE
authors.lastname: Gato
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000032:analysis / Q000235:genetics; D000818:Animals; D000873:Anthracenes / Q000633:toxicity*; D051275:Glucose Transporter Type 4; D005952:Glucose-6-Phosphatase / Q000032:analysis / Q000235:genetics; D007328:Insulin / Q000502:physiology*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction / Q000502:physiology*; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics
chemical_list: D000873:Anthracenes; D051275:Glucose Transporter Type 4; D007328:Insulin; D012333:RNA, Messenger; C495694:Slc2a4 protein, rat; C491408:Socs2 protein, rat; D050826:Suppressor of Cytokine Signaling Proteins; C006593:2-anthramine; D055372:AMP-Activated Protein Kinases; D005952:Glucose-6-Phosphatase