Aug 2007
IRIG: PGC-1/Akt interaction in "Nature" and PPARg regulator in "Cell"
08/25/2007 22:27
Liver produces glucose from amino acids through
gluconeogenesis. If glucose is too much to be
consumed by the peripheral tissues (muscle or fat),
liver will covert the carbohydrate into fatty acids
or triglycerides through hepatic de novo lipogenesis,
resulting in an increase in plasma triglyceride and a
reduction in plasma high-density lipoprotein. This is
demonstrated in human in a new study in PNAS
(See attachment
1).
The hepatic gluconeogenesis and lipogenesis is
regulated by insulin, which inhibits the two
processes through the PI3K/Akt signaling pathway.
In a “Nature” paper, a new event at downstream Akt
is identified for the insulin-mediated inhibition.
Akt2 was found to phosphorylate PGC-1 resulting in
inhibition of PGC-1 function (See attachment
2).
This event leads to shutdown of gene expression in
the programs for gluconeogenesis and lipogenesis
in the liver. PGC-1 is a coactivator of PPARg. In
a “Cell” paper, a small molecule (Harmine) from a
botanical product was found to increase insulin
sensitivity by inducing PPARg gene expression.
Harmine acts by inhibition of the Wnt signaling
pathway (See attachment
3,
2MB in size).
The paper in attachment 1 is recommended by Dr. Zhenqi Liu (University of Virginia School of medicine), and paper in attachment 3 is recommended by Dr. Eugene Chen (University of Michigan Medical Center).
Have a nice weekend.
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
The paper in attachment 1 is recommended by Dr. Zhenqi Liu (University of Virginia School of medicine), and paper in attachment 3 is recommended by Dr. Eugene Chen (University of Michigan Medical Center).
Have a nice weekend.
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
|
RIG: Akt review in Cell
08/04/2007 15:03
Akt (PKB) is a serine
kinase in the signaling pathway of insulin
receptor. In the metabolic branch of the signaling
pathway, Akt mediates insulin signal for GLUT4
translocation, glycogen synthesis (Through
GSK-3) and protein synthesis (through mTOR/S6K).
However, this is only a part of biological
activities of Akt in cells. A recent review in Cell
gives a nice
update on molecules at up- and down-stream of
Akt. By the way, a figure in "Cell
Signaling" website is helpful to get a full
picture of Akt activities. See attached PDF
files.
In the current issue of "Molecular Cell", a new study made a progress in the signaling pathway of FFA. It is known that FFA may induce insulin resistance by targeting IRS-1 in the insulin receptor pathway. This activity is dependent on activation of PKC-JNK kinase axis by FFA. However, the molecules linking PKC to JNK are not completely identified in the FFA pathway. This study shows that a kinase by name of MLK (mixed lineage kinase) mediates PKC signal for JNK activation. Knockout of MLK may reduce Ser307 phosphorylation in IRS-1. 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
In the current issue of "Molecular Cell", a new study made a progress in the signaling pathway of FFA. It is known that FFA may induce insulin resistance by targeting IRS-1 in the insulin receptor pathway. This activity is dependent on activation of PKC-JNK kinase axis by FFA. However, the molecules linking PKC to JNK are not completely identified in the FFA pathway. This study shows that a kinase by name of MLK (mixed lineage kinase) mediates PKC signal for JNK activation. Knockout of MLK may reduce Ser307 phosphorylation in IRS-1. 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
IRIG: Longevity in "Science" and Lipid-ER interaction in "Nature"
08/04/2007 14:54
Insulin resistance in
obesity increases risk for type 2 diabetes and
cardiovascular diseases. These diseases usually
accelerate aging and reduce lifespan. However, a
study in the current issue of Science suggests that
insulin resistance from IRS-2 knockout increased
lifespan together with body weight. The
abstract states that "In mice, less insulin
receptor substrate–2 (Irs2) signaling throughout the
body or just in the brain extended life span up to
18%." The study suggests that the role of insulin
resistance in aging and longevity of obese
subjects is not that simple. See attached paper that is
recommended by Dr. Dixit at
PBRC.
ER stress in obesity has been used to explain insulin resistance. Oversupply of lipid may cause ER stress. However, it is not clear how lipid induces ER stress in obese condition. In the current issue of Nature, an article presents a hypothesis for the regulation of ER function by lipid. See attached paper.
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
ER stress in obesity has been used to explain insulin resistance. Oversupply of lipid may cause ER stress. However, it is not clear how lipid induces ER stress in obese condition. In the current issue of Nature, an article presents a hypothesis for the regulation of ER function by lipid. See attached paper.
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