| First Author | Louet JF | Year | 2010 |
| Journal | Cell Metab | Volume | 12 |
| Issue | 6 | Pages | 606-18 |
| PubMed ID | 21109193 | Mgi Jnum | J:168116 |
| Mgi Id | MGI:4881892 | Doi | 10.1016/j.cmet.2010.11.009 |
| Citation | Louet JF, et al. (2010) The coactivator SRC-1 is an essential coordinator of hepatic glucose production. Cell Metab 12(6):606-18 |
| abstractText | 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/EBPalpha through a feed-forward loop in which SRC-1 used C/EBPalpha 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. |
