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Pharmacodynamic/pharmacogenomic modeling of insulin resistance genes in rat muscle after methylprednisolone treatment: exploring regulatory signaling cascades.

ABSTRACT: Corticosteroids (CS) effects on insulin resistance related genes in rat skeletal muscle were studied. In our acute study, adrenalectomized (ADX) rats were given single doses of 50 mg/kg methylprednisolone (MPL) intravenously. In our chronic study, ADX rats were implanted with Alzet mini-pumps giving zero-order release rates of 0.3 mg/kg/h MPL and sacrificed at various times up to 7 days. Total RNA was extracted from gastrocnemius muscles and hybridized to Affymetrix GeneChips. Data mining and literature searches identified 6 insulin resistance related genes which exhibited complex regulatory pathways. Insulin receptor substrate-1 (IRS-1), uncoupling protein 3 (UCP3), pyruvate dehydrogenase kinase isoenzyme 4 (PDK4), fatty acid translocase (FAT) and glycerol-3-phosphate acyltransferase (GPAT) dynamic profiles were modeled with mutual effects by calculated nuclear drug-receptor complex (DR(N)) and transcription factors. The oscillatory feature of endothelin-1 (ET-1) expression was depicted by a negative feedback loop. These integrated models provide testable quantitative hypotheses for these regulatory cascades.

SUBMITTER: Yao Z

PROVIDER: S-EPMC2733097 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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Pharmacodynamic/pharmacogenomic modeling of insulin resistance genes in rat muscle after methylprednisolone treatment: exploring regulatory signaling cascades.

Yao Zhenling Z Hoffman Eric P EP Ghimbovschi Svetlana S DuBois Debra C DC Almon Richard R RR Jusko William J WJ

Gene regulation and systems biology 20080423

Corticosteroids (CS) effects on insulin resistance related genes in rat skeletal muscle were studied. In our acute study, adrenalectomized (ADX) rats were given single doses of 50 mg/kg methylprednisolone (MPL) intravenously. In our chronic study, ADX rats were implanted with Alzet mini-pumps giving zero-order release rates of 0.3 mg/kg/h MPL and sacrificed at various times up to 7 days. Total RNA was extracted from gastrocnemius muscles and hybridized to Affymetrix GeneChips. Data mining and li ...[more]

PMID: 19787081

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Dataset Information

Pharmacodynamic/pharmacogenomic modeling of insulin resistance genes in rat muscle after methylprednisolone treatment: exploring regulatory signaling cascades.

Publications

Pharmacodynamic/pharmacogenomic modeling of insulin resistance genes in rat muscle after methylprednisolone treatment: exploring regulatory signaling cascades.

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