کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2793294 | 1155130 | 2010 | 13 صفحه PDF | دانلود رایگان |
SummaryGluconeogenesis 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.
► SRC-1 is as a key coordinator of the hepatic gluconeogenic program in vivo
► Selective re-expression of SRC-1 in the liver restores blood glucose levels to a normal range
► Hepatic expression of SRC-1 gene increases during fasting
► SRC-1 modulates the expression of PC via a feed-forward loop involving C/EBPalpha
Journal: - Volume 12, Issue 6, 1 December 2010, Pages 606–618