Apr 2008
IRIG: Gut-brain-liver axis controls liver glucose production
04/24/2008 09:45
Liver is a primary
organ in glucose production in fasting condition.
This liver activity is regulated by Insulin/Glucagon
system. In fasting, glucagon from pancreatic A cells
stimulates the glucose production. In response to
food intake, insulin from pancreatic B cells inhibits
the glucose production. It was controversial about
the role of neural signal in the regulation of
glucose production. The data from dog model suggests
that a nerve signal is not involved in the control of
liver function. In the current "Nature", this
question is addressed in a rat study through vagotomy
or gut vagal deafferentation. The study shows that
there is neural connection between the gut and the
brain. The connection is able to sense lipids in the
gut and pass the signal to liver to inhibit glucose
production. This is an excellent study about
endocrine‑independent mechanism in the control of
glucose homeostasis.
See attached PDF file.
The neuropeptide Y (NYP) is a neurotransmitter with well‑known function in the stimulation of food intake in the brain. In ob/ob mice, an increase in NPY contributes to hyperphagia, and obesity. Its expression in response to emotional stress may explain increased food intake or stress‑related obesity. In "Nature", it is found that a single nucleotide polymorphism (SNP rs16147) located in the promoter region alters NPY expression in vitro, and seems to account for more than half of the variation in expression in vivo. This polymorphism predicts brain responses to emotional and stress challenges. See attached PDF file.
By Jianping at PBRC
‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑
Jianping Ye, MD
Professor of Molecular Biology
Pennington Biomedical Research Center
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
See attached PDF file.
The neuropeptide Y (NYP) is a neurotransmitter with well‑known function in the stimulation of food intake in the brain. In ob/ob mice, an increase in NPY contributes to hyperphagia, and obesity. Its expression in response to emotional stress may explain increased food intake or stress‑related obesity. In "Nature", it is found that a single nucleotide polymorphism (SNP rs16147) located in the promoter region alters NPY expression in vitro, and seems to account for more than half of the variation in expression in vivo. This polymorphism predicts brain responses to emotional and stress challenges. See attached PDF file.
By Jianping at PBRC
‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑
Jianping Ye, MD
Professor of Molecular Biology
Pennington Biomedical Research Center
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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IRIG: TORC2 and PGC-1 in Science and EMBO
04/17/2008 15:59
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