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Titolo:
Peroxisome proliferator-activated receptor subtype-specific regulation of hepatic and peripheral gene expression in the Zucker diabetic fatty rat
Autore:
Dana, SL; Hoener, PA; Bilakovics, JM; Crombie, DL; Ogilvie, KM; Kauffman, RF; Mukherjee, R; Paterniti, JR;
Indirizzi:
Ligand Pharmaceut Inc, Dept Pharmacol, San Diego, CA 92121 USA Ligand Pharmaceut Inc San Diego CA USA 92121 col, San Diego, CA 92121 USA Lilly Res Labs, Dept Cardiovasc Res, Indianapolis, IN USA Lilly Res Labs Indianapolis IN USA Cardiovasc Res, Indianapolis, IN USA
Titolo Testata:
METABOLISM-CLINICAL AND EXPERIMENTAL
fascicolo: 8, volume: 50, anno: 2001,
pagine: 963 - 971
SICI:
0026-0495(200108)50:8<963:PPRSRO>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE; APOLIPOPROTEIN-C-III; MAP KINASE-ACTIVITY; ACYL-COA OXIDASE; INSULIN SIGNAL-TRANSDUCTION; TYROSINE-PHOSPHATASE LAR; PROTEIN-KINASE; RESPONSE ELEMENT; PPAR-ALPHA; NEGATIVE REGULATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Dana, SL Ligand Pharmaceut Inc, Dept Pharmacol, 10275 Sci Ctr Dr, San Diego, CA 92121 USA Ligand Pharmaceut Inc 10275 Sci Ctr Dr San Diego CA USA 92121 USA
Citazione:
S.L. Dana et al., "Peroxisome proliferator-activated receptor subtype-specific regulation of hepatic and peripheral gene expression in the Zucker diabetic fatty rat", METABOLISM, 50(8), 2001, pp. 963-971

Abstract

Fibrates and thiazolidinediones are used clinically to treat hypertriglyceridemia and hyperglycemia, respectively. Fibrates bind to the peroxisome proliferator-activated receptor (PPAR)-alpha, and thiazolidinediones are ligands of PPAR-gamma. These intracellular receptors form heterodimers with retinoid X receptor to modulate gene transcription. To elucidate the target genes regulated by these compounds, we treated Zucker diabetic fatty rats (ZDF) for 15 days with a PPAR-alpha -specific compound, fenofibrate, a PPAR-gamma -specific ligand, rosiglitazone, and a PPAR-alpha/-gamma coagonist, GW2331, and measured the levels of several messenger RNAs (mRNAs) in liver by real-time polymerase chain reaction. All 3 compounds decreased serum glucose and triglyceride levels. Fenofibrate and GW2331 induced expression of acyl-coenzyme A (CoA) oxidase and enoyl-CoA hydratase and reduced apolipoprotein C-III and phosphoenolpyruvate carboxykinase mRNAs. Rosiglitazone modestly increased apolipoprotein C-III mRNA and had no effect on expression of the other 2 genes in the liver but increased the expression of glucose transporter 4 and phosphoenolpyruvate carboxykinase in adipose tissue. We identified a novel target in liver, mitogen-activated phosphokinase phosphatase 1,whose down-regulation by PPAR-alpha agonists may improve insulin sensitivity in that tissue by prolonging insulin responses. The results of these studies suggest that activation of PPAR-alpha as well as PPAR-gamma in therapyfor type 2 diabetes will enhance glucose and triglyceride control by combining actions in hepatic and peripheral tissues. Copyright (C) 2001 by WB. Saunders Company.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/11/20 alle ore 11:42:04