NEW YORK, Jan. 12 /PRNewswire/ -- The Juvenile Diabetes Research

Foundation (JDRF), the world's leading charitable funder of research into type
1 diabetes and its complications, announced today that a new study from a team
of researchers led by Michael Brownlee, M.D., Director of the JDRF
International Center for Diabetic Complications Research, identifies a
molecular link connecting high blood sugar inside cells to the initiation of
diabetic retinopathy.  This finding, reported in the January 27 issue of Cell
(available online at http://www.cell.com as of January 12 at noon), explains how
methylglyoxal (MG), a glucose-derived molecule that is overproduced in cells
damaged by hyperglycemia, turns on a gene called angiopoietin-2, which plays a
central role in the loss of small blood vessels in the retina.
 
In diabetic retinopathy, this loss of small blood vessels causes low
oxygen delivery to parts of the retina, which then compensates by stimulating
new blood vessel growth.  It is the growth of these new vessels that causes
intraretinal bleeding and other problems in the diabetic eye that can
eventually lead to blindness.
 
In diabetic patients only certain cells - those that cannot prevent their
internal glucose levels from rising - are damaged by hyperglycemia.  Dr.
Brownlee and his team discovered that a consequence of high glucose inside a
cell is the overproduction of the free radical superoxide.  This
overproduction causes an increase in the glucose-derived molecule MG, which
then turns on the angiopoietin-2 gene by directly attaching to an inhibitor of
this gene and disabling it, thus resulting in blood vessel damage.  The
group's findings suggest that drugs which result in the suppression of MG and
related molecules in cells may be of benefit in the prevention and treatment
of the retinopathy.  In addition, such drugs might also lead to cancer-
fighting agents due to the fact that they are able to stem the growth of blood
vessels, which feed tumors and may also make tumor cells more susceptible to
destruction by chemotherapy.
 
"Based on our findings, we now believe that by reducing MG levels through
yet-to-be discovered new drugs, we would normalize damaging patterns of gene
expression in complication-prone diabetic cells," said Dr. Brownlee.  "Control
of changes in the concentration of MG also has implications beyond the realm
of retinopathy, since abnormal MG metabolism has been linked to kidney
failure, cancer and malaria.  As such, this discovery has widespread and
important implications, and we're very excited to see where this research will
lead."
 
According to Antony Horton, JDRF's Program Director for Diabetes
Complications, "Methylglyoxal is clearly an important, yet under-examined,
molecule that is implicated in the disease process of two major diabetic
complications:  retinopathy and renal failure. We anticipate that diabetes
researchers will now be able to use this information towards the development
of therapies that will impact the lives of millions of people with diabetes."
About the JDRF International Center for Diabetic Complications Research
JDRF launched the JDRF International Center for Diabetic Complications
Research in 2004, with Dr. Michael Brownlee as director.  With the goal of
developing innovative, effective therapies for preventing the development and
progression of retinopathy, nephropathy, neuropathy, and atherosclerosis in
type 1 diabetes, the center has already discovered a number of promising new
therapies.
 
About JDRF
JDRF (http://www.jdrf.org) was founded in 1970 by the parents of children with
juvenile diabetes - a disease that strikes children suddenly, makes them
insulin dependent for life, and carries the constant threat of devastating
complications.  Since inception, JDRF has provided more than $800 million to
diabetes research worldwide.  More than 80 percent of JDRF' expenditures
directly support research and education about research.  JDRF's mission is
constant:  to find a cure for diabetes and its complications through the
support of research.

*  The coauthors are: Dachun Yao, Tetsuya Taguchi, Takeshi Matsumura,
Diane Edelstein, Ida Giardino and Michael Brownlee from the JDRF
International Center for Diabetic Complications Research at Albert
Einstein College of Medicine, USA;  Naila Ahmed and Paul J. Thornalley
from the Department of Biological Sciences at the University of Essex,
United Kingdom;  Richard Pestell from the Lombardi Cancer Center,
Department of Oncology, Georgetown University, USA; Diane Guntram Suske
from the Institut fuer Molekularbiologie und Tumorforschung,
Philipps-Universitaet Marburg, Germany; Vijay P. Sarthy from the
Department of Ophthalmology, Feinberg School of Medicine, USA and
Hans-Peter Hammes from the V. Med. Klinik-Theodor-Kutzer-Ulfer 1-3,
Germany.

SOURCE Juvenile Diabetes Research Foundation
Web Site: http://www.jdf.org http://www.cell.com