Absence of the SRC-2 coactivator results in a glycogenopathy resembling Von Gierke's disease
AR Chopra, JF Louet, P Saha, J An, F DeMayo, J Xu… - Science, 2008 - science.org
AR Chopra, JF Louet, P Saha, J An, F DeMayo, J Xu, B York, S Karpen, M Finegold…
Science, 2008•science.orgHepatic 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 …
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 …
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 RORα. 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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