Feb 2007
IRIG: New diabetes genes and models for GKS-3b in Nature
02/16/2007 01:03
There are two
interesting papers published online in
Nature. The first one is about identification of
new genes for type 2 diabetes through
genome-wide analysis of gene polymorphism. A couple
of beta-cell specific genes were found to
associate with risk of type 2 diabetes. The
second study describes a new model for analysis
of GSK-3b function in transgenic mice. GSK-3b is
quickly degraded after tagged with a short amino acid
sequence by the name of FRB (FKBP/rapamycin binding).
The degradation leads to inactivation of GSK-3b
in the transgenic mice. Rapamycin is able to
block the degradation in vivo
through specific binding to the tag domain in
the fusion protein of GSK-3b. Following are the links
to these two papers.
ADVANCE ONLINE PUBLICATION
------------------------------
11 February 2007
Article
A genome-wide association study identifies novel risk loci for type 2 diabetes
Robert Sladek et al.
doi:10.1038/nature05616
http://ealerts.nature.com/cgi-bin24/DM/y/ecWf0SohGc0HjB0BL4G0Ea
See also: News and Views by Freimer & Sabatti
http://ealerts.nature.com/cgi-bin24/DM/y/ecWf0SohGc0HjB0BL4H0Eb
Letters
Chemical rescue of cleft palate and midline defects in conditional GSK-3beta mice
Karen J. Liu et al.
doi:10.1038/nature05557
http://ealerts.nature.com/cgi-bin24/DM/y/ecWf0SohGc0HjB0BL4I0Ec
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
Fax: (225) 763-2525
E-mail: yej@pbrc.edu
ADVANCE ONLINE PUBLICATION
------------------------------
11 February 2007
Article
A genome-wide association study identifies novel risk loci for type 2 diabetes
Robert Sladek et al.
doi:10.1038/nature05616
http://ealerts.nature.com/cgi-bin24/DM/y/ecWf0SohGc0HjB0BL4G0Ea
See also: News and Views by Freimer & Sabatti
http://ealerts.nature.com/cgi-bin24/DM/y/ecWf0SohGc0HjB0BL4H0Eb
Letters
Chemical rescue of cleft palate and midline defects in conditional GSK-3beta mice
Karen J. Liu et al.
doi:10.1038/nature05557
http://ealerts.nature.com/cgi-bin24/DM/y/ecWf0SohGc0HjB0BL4I0Ec
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
Fax: (225) 763-2525
E-mail: yej@pbrc.edu
|
IRIG: Obestatin in "Science" and S6K in JCI IRIG: Obestatin in "Science" and S6K in JCI IRIG: Obestatin in "Science" and S6K in JCI IRIG: Obestatin in "Science" and S6K in JCI IRIG: Obestatin in "Science" and S6K in JCI
02/09/2007 07:26
Obestatin,
a peptide derived from the ghrelin precursor, has an
activity opposite to ghrelin for appetite. In the
action mechanism, obestatin was reported to activate
the orphan G protein–coupled receptor GPR39. This
activity of obestatin is under debate in
two technical comments in the current issue of
Science. Below is the titles and
links.
Comment on "Obestatin, a Peptide Encoded by the Ghrelin Gene, Opposes Ghrelin's Effects on Food Intake"
N. Chartrel, R. Alvear-Perez, J. Leprince, X. Iturrioz, A. Reaux-Le Goazigo, V. Audinot, P. Chomarat, F. Coge, O. Nosjean, M. Rodriguez, J. P. Galizzi, J. A. Boutin, H. Vaudry, and C. Llorens-Cortes
http://www.sciencemag.org/cgi/content/abstract/315/5813/766c?etoc
p. 766
Response to Comment on "Obestatin, a Peptide Encoded by the Ghrelin Gene, Opposes Ghrelin's Effects on Food Intake"
Jian V. Zhang, Cynthia Klein, Pei-Gen Ren, Stefan Kass, Luc Ver Donck, Dieder Moechars, and Aaron J. W. Hsueh
http://www.sciencemag.org/cgi/content/abstract/315/5813/766d?etoc
p. 766
S6K is a signaling enzyme in the insulin receptor pathway. S6K has been shown to induce IRS-1 serine phosphorylation (at Ser307 in mouse or Ser312 in human) for insulin resistance. S6K knockout mice are resistant to obesity and insulin resistance. In the current JCI, mice with increased S6K activity have "Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2". Below are titles and links of the paper and relative comment in JCI.
Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2Olivier Le Bacquer, Emmanuel Petroulakis, Sabina Paglialunga, Francis Poulin, Denis Richard, Katherine Cianflone, and Nahum Sonenberg J. Clin. Invest. 2007; 117:387-396. [Abstract] [Full Text] [PDF]
A link between protein translation and body weightLiangyou Rui J. Clin. Invest. 2007; 117:310-313. [Abstract] [Full Text] [PDF]
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 Fax: (225) 763-2525 E-mail: yej@pbrc.edu
Comment on "Obestatin, a Peptide Encoded by the Ghrelin Gene, Opposes Ghrelin's Effects on Food Intake"
N. Chartrel, R. Alvear-Perez, J. Leprince, X. Iturrioz, A. Reaux-Le Goazigo, V. Audinot, P. Chomarat, F. Coge, O. Nosjean, M. Rodriguez, J. P. Galizzi, J. A. Boutin, H. Vaudry, and C. Llorens-Cortes
http://www.sciencemag.org/cgi/content/abstract/315/5813/766c?etoc
p. 766
Response to Comment on "Obestatin, a Peptide Encoded by the Ghrelin Gene, Opposes Ghrelin's Effects on Food Intake"
Jian V. Zhang, Cynthia Klein, Pei-Gen Ren, Stefan Kass, Luc Ver Donck, Dieder Moechars, and Aaron J. W. Hsueh
http://www.sciencemag.org/cgi/content/abstract/315/5813/766d?etoc
p. 766
S6K is a signaling enzyme in the insulin receptor pathway. S6K has been shown to induce IRS-1 serine phosphorylation (at Ser307 in mouse or Ser312 in human) for insulin resistance. S6K knockout mice are resistant to obesity and insulin resistance. In the current JCI, mice with increased S6K activity have "Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2". Below are titles and links of the paper and relative comment in JCI.
Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2Olivier Le Bacquer, Emmanuel Petroulakis, Sabina Paglialunga, Francis Poulin, Denis Richard, Katherine Cianflone, and Nahum Sonenberg J. Clin. Invest. 2007; 117:387-396. [Abstract] [Full Text] [PDF]
A link between protein translation and body weightLiangyou Rui J. Clin. Invest. 2007; 117:310-313. [Abstract] [Full Text] [PDF]
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 Fax: (225) 763-2525 E-mail: yej@pbrc.edu
IRIG: PKC regulation of mitochondria in Science
02/07/2007 08:52
Protein kinase C
(PKC) may have dual activities in the regulation of
glucose and fatty acid metabolism. When it is
over-activated by DAG (Diaglyceride), PKC may induce
insulin resistance by increasing serine
phosphorylation of insulin receptor as well as
insulin receptor substrate 1 (IRS-1). This happens
when DAG level is increased in cells under
obesity or lipid infusion. Oxidative stress
from hyperglycemia also induces PKC
over-activation.
On the other side, inactivation of PKC in mice may lead to reduction in energy expenditure promoting obesity and insulin resistance on high fat diet. The molecular basis of this activity remains unknown for PKC. A study in the current issue of Science may provide a possible mechanism. In the investigation of aging-related protein p66Shr, PKC was shown to activate this protein through phosphorylation, leading to production of free radicals in the mitochondria. This activity of PKC was demonstrated in an extreme condition where the cells were treated with H2O2 for apoptosis. Although regulation of the mitochondrial function by PKC was used to explain apoptosis in the study, the linkage of PKC to p66Shr suggests that in the physiological condition, PKC may use this channel to stimulate metabolism of glucose and fatty acids in the mitochondria. Mitochondrial production of free radicals is associated with metabolism of glucose or fatty acids. In obesity, PKC may use this linkage to induce mitochondrial dysfunction. These possibilities are not discussed in the paper, but it is worth to read it. Attached is PDF file of this paper.
In the current issue of Nature Medicine, there are several interesting papers related to molecular physiology related to metabolic syndrom. Below is the list.
Brain glucose metabolism controls the hepatic secretion of triglyceride-rich lipoproteins pp171 - 180
Tony K T Lam et al.
10.1038/nm1540
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLcW0Eu
Article: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLcX0Ev
Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity pp189 - 197
Jane A Leopold et al.
10.1038/nm1545
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLca0E5
Article: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLcb0E6
Angiotensin II type 1 receptor blockade attenuates TGF-[beta]-induced failure of muscle regeneration in multiple myopathic states pp204 - 210
Ronald D Cohn et al.
10.1038/nm1536
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLce0EA
Article: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLcf0EB
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
Fax: (225) 763-2525
E-mail: yej@pbrc.edu
On the other side, inactivation of PKC in mice may lead to reduction in energy expenditure promoting obesity and insulin resistance on high fat diet. The molecular basis of this activity remains unknown for PKC. A study in the current issue of Science may provide a possible mechanism. In the investigation of aging-related protein p66Shr, PKC was shown to activate this protein through phosphorylation, leading to production of free radicals in the mitochondria. This activity of PKC was demonstrated in an extreme condition where the cells were treated with H2O2 for apoptosis. Although regulation of the mitochondrial function by PKC was used to explain apoptosis in the study, the linkage of PKC to p66Shr suggests that in the physiological condition, PKC may use this channel to stimulate metabolism of glucose and fatty acids in the mitochondria. Mitochondrial production of free radicals is associated with metabolism of glucose or fatty acids. In obesity, PKC may use this linkage to induce mitochondrial dysfunction. These possibilities are not discussed in the paper, but it is worth to read it. Attached is PDF file of this paper.
In the current issue of Nature Medicine, there are several interesting papers related to molecular physiology related to metabolic syndrom. Below is the list.
Brain glucose metabolism controls the hepatic secretion of triglyceride-rich lipoproteins pp171 - 180
Tony K T Lam et al.
10.1038/nm1540
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLcW0Eu
Article: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLcX0Ev
Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity pp189 - 197
Jane A Leopold et al.
10.1038/nm1545
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLca0E5
Article: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLcb0E6
Angiotensin II type 1 receptor blockade attenuates TGF-[beta]-induced failure of muscle regeneration in multiple myopathic states pp204 - 210
Ronald D Cohn et al.
10.1038/nm1536
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLce0EA
Article: http://ealerts.nature.com/cgi-bin24/DM/y/ecOm0SohGc0HjT0BLcf0EB
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
Fax: (225) 763-2525
E-mail: yej@pbrc.edu