In:
American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 298, No. 6 ( 2010-06), p. E1210-E1218
Abstract:
Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a key regulator of cellular energy metabolism and regulates processes such as adaptive thermogenesis, hepatic gluconeogenesis, fatty acid oxidation, and mitochondrial biogenesis by coactivating numerous nuclear receptors and transcription factors. Here, we demonstrate the presence of the ERRα binding site in the regulatory sequence of the glucokinase gene and that PGC-1α coactivates ERRα to stimulate the transcription of glucokinase. Simultaneous overexpression of PGC-1α and ERRα potently induced the glucokinase gene expression and its enzymatic activity in primary hepatocytes; however, expression of either PGC-1α or ERRα alone had no significant effect. Electrophoretic mobility shift and chromatin immunoprecipitation assays revealed the interaction of ERRα with the glucokinase promoter. Finally, the knockdown of endogenous ERRα with specific siRNA (siERRα) or pharmacological inhibition of ERRα with XCT790 attenuated insulin-induced glucokinase expression. Taken together, this research identifies glucokinase as a novel target of PGC-1α/ERRα and underscores the regulatory function of ERRα in insulin-dependent enzyme regulation.
Type of Medium:
Online Resource
ISSN:
0193-1849
,
1522-1555
DOI:
10.1152/ajpendo.00633.2009
Language:
English
Publisher:
American Physiological Society
Publication Date:
2010
detail.hit.zdb_id:
1477331-4
SSG:
12
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