Mar 2008
IRIG: O-GlcNAc and PGC-1 in Nature
03/09/2008 20:20
The negative-feedback loop in the insulin signaling
pathway is a framework for the concept of
post-receptor signaling defect theory, which
represents the mainstream views of insulin
resistance. In the school, inhibition of insulin
receptor substrates (IRSs) by serine/threonine
kinases is the core. Many molecular hypotheses for
insulin resistance, such as inflammation, ER stress,
mitochondrial dysfunction, oxidative stress,
hyperinsulinemia, and hypoadiponectinemia, are built
on the core. A new study in Nature enriched the
theory by demonstration that insulin may promote
IRS-1 inhibition by increasing glycocylation of
IRS-1. The enzyme O-GlcNAc transferase (OGT) mediates
this activity of insulin. This paper is recommended
by Dr. Marina Bouché at the University of Rome,
Italy. (See PDF file
attached).
PGC-1a is another “star” molecule like SIRT1. PGC-1a is a transcription coactivator originally identified in the study of PPARg. PGC-1a is involved in glucose homeostasis, mitochondrial biogenesis, circadian rhythm, and energy expenditure. A new study in Nature shows that PGC-1a is involved in protection of microcirculation from ischemia damage by promoting angiogenesis. The mechanism is induction of VEGF expression by PGC-1a. (See PDF file attached).
By the way, the “Insight” section of Nature is focused on Cardiovascular disease in this issue. It contains eight excellent reviews about different aspects of CVDs. Here is the link: http://www.nature.com/nature/index.html
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
PGC-1a is another “star” molecule like SIRT1. PGC-1a is a transcription coactivator originally identified in the study of PPARg. PGC-1a is involved in glucose homeostasis, mitochondrial biogenesis, circadian rhythm, and energy expenditure. A new study in Nature shows that PGC-1a is involved in protection of microcirculation from ischemia damage by promoting angiogenesis. The mechanism is induction of VEGF expression by PGC-1a. (See PDF file attached).
By the way, the “Insight” section of Nature is focused on Cardiovascular disease in this issue. It contains eight excellent reviews about different aspects of CVDs. Here is the link: http://www.nature.com/nature/index.html
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
|
IRIG: Studies in Nature, Science and Cell
03/09/2008 20:19
The product of longevity gene SIRT1 has been a “Star”
molecular in the past five years. Most of papers
about SIRT1 are published in the top journals. This
reflects the strong desire of the scientific
community for understanding molecular mechanism of
ageing. Now, SIRT1 is known to regulate
carcinogenesis, energy metabolism and embryo
development. All of these activities are “good” for
longevity. The precise control of SIRT1 activity is
of interesting. In Nature, two recent studies suggest
that SIRT1 activity is controlled by breast
cancer-related gene. DBC1 (deleted in breast cancer
1) is shown to be a native inhibitor of SIRT1 in
human cells.
See attached
PDF.
These papers are recommended by Dr. Eric Ravussin
at PBRC.
Control of blood glucose is a major work in the treatment of diabetes. However, the degree of reducing blood glucose is controversial. To clarify the issue, the best way is clinical trial though it is very expensive. Now, a report in Science suggests that reducing blood glucose to the normal level is bad in long term as the diabetes patients died at a higher rate in the clinical trial. See PDF attached. This is recommended by Dr. Zhong Yun at the Yale University.
Hyperglycemia leads to insulin resistance. The molecular mechanism is related to oxidative stress. In Cell, a study shows that glucose may induce insulin resistance in muscle by reducing diacylglycerol (DAG) kinase. This leads to an increase in DAG and PKC activity for insulin resistance. Though it is well known that glucose increases DAG level, people believe that it is a result of enhanced DAG production. This study suggests that a reduction in DAG metabolism contributes to the increase. See PDF attached.
An interesting paper about Ghrelin at: http://www.sciencedirect.com/science/article/B6WSN-4RSJ9JW-C/2/d1fb4471d9bd18c50fc64043372e929c
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
Control of blood glucose is a major work in the treatment of diabetes. However, the degree of reducing blood glucose is controversial. To clarify the issue, the best way is clinical trial though it is very expensive. Now, a report in Science suggests that reducing blood glucose to the normal level is bad in long term as the diabetes patients died at a higher rate in the clinical trial. See PDF attached. This is recommended by Dr. Zhong Yun at the Yale University.
Hyperglycemia leads to insulin resistance. The molecular mechanism is related to oxidative stress. In Cell, a study shows that glucose may induce insulin resistance in muscle by reducing diacylglycerol (DAG) kinase. This leads to an increase in DAG and PKC activity for insulin resistance. Though it is well known that glucose increases DAG level, people believe that it is a result of enhanced DAG production. This study suggests that a reduction in DAG metabolism contributes to the increase. See PDF attached.
An interesting paper about Ghrelin at: http://www.sciencedirect.com/science/article/B6WSN-4RSJ9JW-C/2/d1fb4471d9bd18c50fc64043372e929c
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