The peptide hormone glucagon stimulates hepatic @entity413 output, and its levels in the blood are elevated in @entity6 . The nuclear receptor peroxisome proliferator-activated receptor-gamma ( @entity6864 ) has essential roles in @entity413 homeostasis, and @entity12585 @entity6864 agonists are clinically important antidiabetic drugs. As part of their antidiabetic effect, @entity12721 such as @entity6170 have been shown to inhibit glucagon gene transcription through binding to @entity6864 and inhibition of the transcriptional activity of @entity6484 that is required for cell-specific activation of the glucagon gene. However, how @entity12721 and @entity6864 inhibit @entity6484 activity at the glucagon promoter remained unknown. After transient transfection of a glucagon promoter-reporter fusion gene into a glucagon-producing pancreatic islet alpha-cell line, ligand-bound @entity6864 was found in the present study to inhibit glucagon gene transcription also after deletion of its DNA-binding domain. Like @entity6864 ligands, also @entity13351 ( @entity13351 ) agonists inhibited glucagon gene transcription in a @entity6864 -dependent manner. In @entity2041 transferase pull-down assays, the ligand-bound @entity6864 - @entity13351 heterodimer bound to the transactivation domain of @entity6484 . This interaction depended on the presence of the ligand and @entity13351 , but it was independent of the @entity6864 DNA-binding domain. Chromatin immunoprecipitation experiments showed that @entity6864 is recruited to the @entity6484 -binding proximal glucagon promoter. Taken together, the results of the present study support a model in which a ligand-bound @entity6864 - @entity13351 heterodimer physically interacts with promoter-bound @entity6484 to inhibit glucagon gene transcription. These data define @entity6484 as a novel physical target of @entity6864 - @entity13351 .

A peroxisome proliferator-activated receptor gamma- XXXX heterodimer physically interacts with the transcriptional activator @entity6484 to inhibit glucagon gene transcription.

@entity13351 :: ('6256', 'Gene') :: ['retinoid X receptor', 'RXR'] @entity6 :: ('MESH:D003920', 'Disease') :: ['type 2 diabetes mellitus'] @entity12585 :: ('MESH:C089946', 'Chemical') :: ['thiazolidinedione'] @entity2041 :: ('MESH:D005978', 'Chemical') :: ['glutathione'] @entity12721 :: ('MESH:D045162', 'Chemical') :: ['thiazolidinediones'] @entity6484 :: ('5080', 'Gene') :: ['PAX6'] @entity6170 :: ('MESH:C089730', 'Chemical') :: ['rosiglitazone'] @entity413 :: ('MESH:D005947', 'Chemical') :: ['glucose'] @entity6864 :: ('5468', 'Gene') :: ['PPARgamma']
@entity13351 :: (6256,Gene) :: ['retinoid X receptor']
