IRIG: TORC2 and PGC-1 in Science and EMBO
04/17/2008 16:59
TORC2 and PGC‑1 are two
nuclear coactivators in the control of glucose
metabolism. TORC2 that was highlighted in IRIG
several times promotes gluconeogenesis in liver
through CREB, a transcription factor that activates
PEPCK and G6Pase expression for glucose production.
TORC2 activity is regulated by serine
phosphorylation. In the
Science,
TORC2 (also named as CRTC2) was found to promote
hepatic gluconeogenesis in response to glucose or
related analogs (mannose, fructose, or galactose).
The mechanism is modification of TORC2 by
O‑glycosylation, which is triggered by glucose or
its analogs. The importance of signaling protein
modification by glycosylation is demonstrated
again in the regulation of glucose metabolism.
Modification of IRS‑1 by glycosylation was
highlighted in IRIG earlier.
PGC‑1 is a downstream target of TORC2, which promotes PGC‑1a expression through CREB. Activity of PGC‑1a is regulated by expression, phosphorylation, and acetylation. Deacetylation of PGC‑1a by SIRT1 is involved in induction of hepatic gluconeogenesis. PGC‑1a also stimulates mitochondrial function through gene transcription. In EMBO, PGC‑1a is shown to enhance fatty acid oxidation in muscle through induction of mitochondrial function. The study suggests that in response to fasting, PGC‑1a is activated in muscle by SIRT1‑medaited deacetylation. This paper is recommended by Dr. Eric Ravussin at PBRC.
These two studies provide new evidence that epigenetic signaling pathways are important in the regulation of glucose metabolism. Attached are PDF files of the two papers. Previous posts in IRIG can be found at: http://c-ada.org
By Jianping at PBRC
‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑
Jianping Ye, MD
Professor of Molecular Biology
Pennington Biomedical Research Center (PBRC)
Louisiana State University System
6400 Perkins Road
Baton Rouge, LA 70808
Phone: (225)763‑3163
E‑mail: yej@pbrc.edu
Webpage: http://labs.pbrc.edu/generegulation/index.htm
PGC‑1 is a downstream target of TORC2, which promotes PGC‑1a expression through CREB. Activity of PGC‑1a is regulated by expression, phosphorylation, and acetylation. Deacetylation of PGC‑1a by SIRT1 is involved in induction of hepatic gluconeogenesis. PGC‑1a also stimulates mitochondrial function through gene transcription. In EMBO, PGC‑1a is shown to enhance fatty acid oxidation in muscle through induction of mitochondrial function. The study suggests that in response to fasting, PGC‑1a is activated in muscle by SIRT1‑medaited deacetylation. This paper is recommended by Dr. Eric Ravussin at PBRC.
These two studies provide new evidence that epigenetic signaling pathways are important in the regulation of glucose metabolism. Attached are PDF files of the two papers. Previous posts in IRIG can be found at: http://c-ada.org
By Jianping at PBRC
‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑
Jianping Ye, MD
Professor of Molecular Biology
Pennington Biomedical Research Center (PBRC)
Louisiana State University System
6400 Perkins Road
Baton Rouge, LA 70808
Phone: (225)763‑3163
E‑mail: yej@pbrc.edu
Webpage: http://labs.pbrc.edu/generegulation/index.htm
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