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    Biochem Biophys Res Commun. 1996 Jul 16;224(2):431-7.

    Molecular cloning, expression and characterization of human peroxisome proliferator activated receptors gamma 1 and gamma 2.

    Elbrecht A, Chen Y, Cullinan CA, Hayes N, Leibowitz M, Moller DE, Berger J.

    Department of Molecular Endocrinology, Merck Research Laboratories, Rahway, New Jersey 07065, USA.

    We describe the molecular cloning and expression of cDNAs encoding human PPAR gamma 1 and PPAR gamma 2. Our sequences are distinct from the published sequence at 3 positions, resulting in nonconservative amino acid substitutions. In humans, PPAR gamma mRNA is expressed in spleen, bone marrow, liver, testis, skeletal muscle and brain, in addition to fat. Three thiazolidinediones were found to 1) displace a radiolabeled thiazolidinedione from both receptors with essentially the same IC50s and 2) to transactivate both PPAR gamma isoforms with similar EC50s in transient cotransfection assays utilizing the adipocyte-specific aP2 promoter. Saturating concentrations of these 3 thiazolidinediones altered the conformation of in vitro synthesized PPAR gamma protein producing a 27 kDa protease-resistant fragment. These results indicate that the antidiabetic effects of thiazolidinediones in humans are likely to be mediated via binding to and transactivation of PPAR gamma 1 and gamma 2.

    PMID: 8702406 [PubMed - indexed for MEDLINE]

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    Cited by 15 PubMed Central articles

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