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Cell Metab. 2010 Dec 1;12(6):606-18. doi: 10.1016/j.cmet.2010.11.009.

The coactivator SRC-1 is an essential coordinator of hepatic glucose production.

Author information

1
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.

Abstract

Gluconeogenesis makes a major contribution to hepatic glucose production, a process critical for survival in mammals. In this study, we identify the p160 family member, SRC-1, as a key coordinator of the hepatic gluconeogenic program in vivo. SRC-1-null mice displayed hypoglycemia secondary to a deficit in hepatic glucose production. Selective re-expression of SRC-1 in the liver restored blood glucose levels to a normal range. SRC-1 was found induced upon fasting to coordinate in a cell-autonomous manner, the gene expression of rate-limiting enzymes of the gluconeogenic pathway. At the molecular level, the main role of SRC-1 was to modulate the expression and the activity of C/EBPα through a feed-forward loop in which SRC-1 used C/EBPα to transactivate pyruvate carboxylase, a crucial gene for initiation of the gluconeogenic program. We propose that SRC-1 acts as a critical mediator of glucose homeostasis in the liver by adjusting the transcriptional activity of key genes involved in the hepatic glucose production machinery.

PMID:
21109193
PMCID:
PMC3024581
DOI:
10.1016/j.cmet.2010.11.009
[Indexed for MEDLINE]
Free PMC Article

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