Juvenile Diabetes Research Foundation-Funded Researchers Discover Molecular Link Between Hyperglycemia And Retinopathy

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 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 (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.

Juvenile Diabetes Research Foundation

CONTACT: Eileen Brangan, National Manager, Media Relations, JuvenileDiabetes Research Foundation, +1-212-479-7577, or ebrangan@jdrf.org

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