期刊
SCIENCE
卷 322, 期 5906, 页码 1395-1399出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1164847
关键词
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资金
- National Institute of Diabetes and Digestive and Kidney Diseases [PO1 DK59820]
- NIH [HL51586, DK58242, PO1 DK58398]
- Nuclear Receptor Signaling Atlas ( NURSA) [U19 DK062434]
- Welch Foundation
Hepatic glucose production is critical for basal brain function and survival when dietary glucose is unavailable. Glucose- 6- phosphatase (G6Pase) is an essential, rate- limiting enzyme that serves as a terminal gatekeeper for hepatic glucose release into the plasma. Mutations in G6Pase result in Von Gierke's disease ( glycogen storage disease-1a), a potentially fatal genetic disorder. We have identified the transcriptional coactivator SRC-2 as a regulator of fasting hepatic glucose release, a function that SRC- 2 performs by controlling the expression of hepatic G6Pase. SRC- 2 modulates G6Pase expression directly by acting as a coactivator with the orphan nuclear receptor ROR alpha. In addition, SRC- 2 ablation, in both a whole- body and liver- specific manner, resulted in a Von Gierke's disease phenotype in mice. Our results position SRC- 2 as a critical regulator of mammalian glucose production.
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