Ozone induces glucose intolerance and systemic metabolic effects in young and aged brown Norway rats.

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Ozone induces glucose intolerance and systemic metabolic effects in young and aged brown Norway rats.

Bass V, Gordon CJ, Jarema KA, Macphail RC, Cascio WE, Phillips PM, Ledbetter AD, Schladweiler MC, Andrews D, Miller D, Doerfler DL, Kodavanti UP.

Journal		Toxicol Appl Pharmacol.
Species
Analytes Measured		A2M , Adiponectin , AGP , Glucagon , IL-6 , Insulin , Leptin
Matrix Tested		Serum

Year		2013
Volume		273
Page Numbers		551-560
Application		Cytokines and Chemokines , Metabolic , Toxicology

Abstract

Air pollutants have been associated with increased diabetes in humans. We hypothesized that ozone would impair glucose homeostasis by altering insulin signaling and/or endoplasmic reticular (ER) stress in young and aged rats. One, 4, 12, and 24month old Brown Norway (BN) rats were exposed to air or ozone, 0.25 or 1.0ppm, 6h/day for 2days (acute) or 2d/week for 13weeks (subchronic). Additionally, 4month old rats were exposed to air or 1.0ppm ozone, 6h/day for 1 or 2days (time-course). Glucose tolerance tests (GTT) were performed immediately after exposure. Serum and tissue biomarkers were analyzed 18h after final ozone for acute and subchronic studies, and immediately after each day of exposure in the time-course study. Age-related glucose intolerance and increases in metabolic biomarkers were apparent at baseline. Acute ozone caused hyperglycemia and glucose intolerance in rats of all ages. Ozone-induced glucose intolerance was reduced in rats exposed for 13weeks. Acute, but not subchronic ozone increased α2-macroglobulin, adiponectin and osteopontin. Time-course analysis indicated glucose intolerance at days 1 and 2 (2>1), and a recovery 18h post ozone. Leptin increased day 1 and epinephrine at all times after ozone. Ozone tended to decrease phosphorylated insulin receptor substrate-1 in liver and adipose tissues. ER stress appeared to be the consequence of ozone induced acute metabolic impairment since transcriptional markers of ER stress increased only after 2days of ozone. In conclusion, acute ozone exposure induces marked systemic metabolic impairments in BN rats of all ages, likely through sympathetic stimulation.

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Human Insulin Antibody Insulin \| Human, Non-human primate, Canine
V-PLEX Metabolic Panel 1 Human Kit C-Peptide, GIP (active), GLP-1 (active), Glucagon, Insulin, Leptin, PP \| Human Multiplex
V-PLEX Metabolic Panel 1 Canine Kit GIP (active), GLP-1 (active), Glucagon, Insulin \| Canine Multiplex
V-PLEX Plus Metabolic Panel 1 NHP Kit C-Peptide, GIP (active), GLP-1 (active), Glucagon, Insulin, PP \| Non-human primate Multiplex
V-PLEX Plus Metabolic Panel 1 Mouse Kit GLP-1 (active), Glucagon \| Mouse Multiplex
V-PLEX Plus Metabolic Panel 1 Human Kit C-Peptide, GIP (active), GLP-1 (active), Glucagon, Insulin, Leptin, PP \| Human Multiplex
V-PLEX Plus Metabolic Panel 1 Canine Kit GIP (active), GLP-1 (active), Glucagon, Insulin \| Canine Multiplex
V-PLEX Metabolic Panel 1 Rat Kit GIP (active), GLP-1 (active), Glucagon \| Rat Multiplex
V-PLEX Metabolic Panel 1 NHP Kit C-Peptide, GIP (active), GLP-1 (active), Glucagon, Insulin, PP \| Non-human primate Multiplex
V-PLEX Metabolic Panel 1 Mouse Kit GLP-1 (active), Glucagon \| Mouse Multiplex
V-PLEX Plus Metabolic Panel 1 Rat Kit GIP (active), GLP-1 (active), Glucagon \| Rat Multiplex
V-PLEX Plus Human Insulin Kit Insulin \| Human, Non-human primate, Canine Singleplex
V-PLEX Plus Glucagon Kit Glucagon \| Human, Mouse, Rat, Non-human primate, Canine Singleplex
V-PLEX Human Insulin Kit Insulin \| Human, Non-human primate, Canine Singleplex
V-PLEX Glucagon Kit Glucagon \| Human, Mouse, Rat, Non-human primate, Canine Singleplex
V-PLEX Plus Human Leptin Kit Leptin \| Human Singleplex
V-PLEX Human Leptin Kit Leptin \| Human Singleplex
V-PLEX Viral Panel 3 NHP Kit IFN-γ, IL-1β, IL-5, IL-6, IL-8, IL-10 \| Non-human primate Multiplex
V-PLEX Viral Panel 3 Human Kit IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, TNF-α \| Human Multiplex
V-PLEX Plus Viral Panel 3 NHP Kit IFN-γ, IL-1β, IL-5, IL-6, IL-8, IL-10 \| Non-human primate Multiplex
V-PLEX Plus Viral Panel 3 Human Kit IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, TNF-α \| Human Multiplex
U-PLEX Viral Combo 1 (NHP) G-CSF, GM-CSF, IFN-α2a, IFN-γ, IL-1β, IL-1RA, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IP-10, MCP-1, MIP-1α, TNF-α, VEGF-A \| Non-human primate Multiplex
U-PLEX Viral Combo 1 (human) G-CSF, GM-CSF, IFN-α2a, IFN-β, IFN-γ, IL-1β, IL-1RA, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IP-10, MCP-1, MIP-1α, TNF-α, VEGF-A \| Human Multiplex
V-PLEX Viral Panel 2 NHP Kit IFN-γ, IL-1β, IL-6, IL-8, IL-10 \| Non-human primate Multiplex
V-PLEX Viral Panel 2 Human Kit IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-α \| Human Multiplex
V-PLEX Viral Panel 1 NHP Kit IL-1β, IL-6, IL-8 \| Non-human primate Multiplex
V-PLEX Viral Panel 1 Human Kit IL-1β, IL-6, IL-8, TNF-α \| Human Multiplex
V-PLEX Plus Viral Panel 2 NHP Kit IFN-γ, IL-1β, IL-6, IL-8, IL-10 \| Non-human primate Multiplex
V-PLEX Plus Viral Panel 2 Human Kit IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-α \| Human Multiplex
V-PLEX Plus Viral Panel 1 NHP Kit IL-1β, IL-6, IL-8 \| Non-human primate Multiplex
V-PLEX Plus Viral Panel 1 Human Kit IL-1β, IL-6, IL-8, TNF-α \| Human Multiplex
U-PLEX Human IL-6 Assay IL-6 \| Human Singleplex
U-PLEX Mouse IL-6 Assay IL-6 \| Mouse Singleplex
U-PLEX NHP IL-6 Assay IL-6 \| Non-human primate Singleplex
U-PLEX Human Leptin Assay Leptin \| Human Singleplex
U-PLEX Human Insulin Assay Insulin \| Human Singleplex
U-PLEX Human Glucagon Assay Glucagon \| Human Singleplex
U-PLEX Rat Leptin Assay Leptin \| Rat Singleplex
U-PLEX Rat Insulin Assay Insulin \| Rat Singleplex
U-PLEX Rat Glucagon Assay Glucagon \| Rat Singleplex
U-PLEX Mouse Leptin Assay Leptin \| Mouse Singleplex
U-PLEX Mouse Insulin Assay Insulin \| Mouse Singleplex
U-PLEX Mouse Glucagon Assay Glucagon \| Mouse Singleplex
R-PLEX Human AGP Assay AGP \| Human Singleplex
R-PLEX Mouse Adiponectin Assay Adiponectin \| Mouse Singleplex
R-PLEX Rat IL-6 Assay IL-6 \| Rat Singleplex
R-PLEX Rat Adiponectin Assay Adiponectin \| Rat Singleplex
U-PLEX Custom Metabolic Group 1 (rat) Assays Rat Multiplex
U-PLEX Custom Metabolic Group 1 (mouse) Assays Mouse Multiplex
U-PLEX Gut Hormone Combo 1 (mouse) Ghrelin (active), GLP-1 (active), Glucagon, Insulin, Leptin, PYY (total) \| Mouse Multiplex
U-PLEX Adipokine Combo 1 (mouse) BDNF, IL-1β, IL-6, IL-10, Insulin, Leptin, MCP-1, TNF-α \| Mouse Multiplex
U-PLEX Metabolic Hormones Combo 1 (rat) C-Peptide, Ghrelin (active), GLP-1 (active), Glucagon, Insulin, Leptin, PYY (total) \| Rat Multiplex
U-PLEX Metabolic Combo 1 (rat) BDNF, C-Peptide, FGF-21, Ghrelin (active), Ghrelin (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, Insulin, Leptin, PYY (total) \| Rat Multiplex
U-PLEX Metabolic Combo 1 (mouse) BAFF, BDNF, C-Peptide, FGF-21, Ghrelin (active), Ghrelin (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, Insulin, Leptin, PYY (total) \| Mouse Multiplex
U-PLEX Metabolic 3-Plex Combo 2 (rat) GLP-1 (active), Glucagon, Insulin \| Rat Multiplex
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Ozone induces glucose intolerance and systemic metabolic effects in young and aged brown Norway rats.

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