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[IP] Fwd: JDRF Research E-Newsletter #27

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Subject: JDRF Research E-Newsletter #27
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December 5, 2002
No. 27


1. Embryonic Stem Cells Reverse Diabetes in Mice
2. Blood Pressure Drug Blocks Factors Linked to Kidney Disease
3. New Focus on Early Changes in Diabetic Retinopathy
4. Advances in Microarray Technology for Genetic Research 
5. U.K. Releases Report on Diabetes Research Opportunities 

1. Embryonic Stem Cells Reverse Diabetes in Mice
For the first time, scientists succeeded in converting embryonic stem cells into insulin-producing tissue that kept diabetic mice alive.  The research was conducted at Stanford University School of Medicine and reported online in the November 19 early edition of the Proceedings of the National Academy of Sciences. Two researchers on the Stanford team are supported by grants from JDRF.

The scientists used special chemicals to transform undifferentiated (non-specialized) embryonic stem cells in mice into cell masses that resemble islets found in the mouse pancreas. Experiments in test tubes showed that these cell masses could make insulin. The scientists then grafted some of the insulin-producing tissue into diabetic mice. The transplanted tissue produced insulin in response to the high glucose levels in the animals, and kept the mice alive. When the grafts were removed a few weeks later, the mice died of diabetes, proving that the transplanted tissue was what had kept them alive. 

The transplanted tissue produced insulin at only 10 to 20 percent of the levels in normal mice, and it did not secrete some of the other hormones or factors made by a normal beta cell. Researchers are not certain what role these other factors might play in regulating metabolism or how necessary they are to preventing diabetes. The feat, while an important proof of principle, is not yet ready for testing in humans.  JDRF Chief Scientific Officer Robert Goldstein told the Associated Press that being able to take embryonic stem cells and reverse diabetes is an extremely important observation, but he emphasized that translating the mouse data into therapies for humans could be a long and difficult process.

To read the abstract for this paper, click below:

JDRF has taken a global leadership role in stem cell research, because it has the potential to provide an unlimited supply of islet cells; as a result, islet transplantation could become a therapy for all people with type 1 diabetes.  Developing alternative islet sources is one of two goals recently identified by JDRF as a critical funding focus.  To read JDRFs backgrounder on important changes in its research portfolio and research funding mechanisms changes, click below:

2. Blood Pressure Drug Blocks Factors Linked to Kidney Disease
People with type 1 diabetes are at an increased risk for developing kidney disease, known as diabetic nephropathy. The high levels of glucose in the blood lead to the formation of harmful products called Advanced Glycation Endproducts (AGEs), which cause damage to the vulnerable small blood vessels that feed the kidneys. High blood pressure speeds up the damage to these vessels and the kidney in general, so drugs used for this condition are encouraged to prevent or delay kidney disease.

One type of blood-pressure drug known as an Angiotensin-Converting Enzyme (ACE) inhibitor has been shown in studies to slow the progression of kidney disease significantly in patients with type 1 diabetes. The ACE inhibitors interrupt a key biological pathway called the renin-angiotensin system (RAS), which helps regulate blood flow by constricting and relaxing the vessels. While researchers knew ACE inhibitors helped against diabetic nephropathy, they were uncertain of the exact mechanism. Did blocking RAS somehow prevent AGEs from building up?

A team of researchers in Melbourne, Australia, tested the effect of one ACE inhibitor, ramipril, on the formation of AGEs in rats with diabetes. The scientists found that ramipril stops the buildup of AGEs in the animals. The rats also had far less damage to their kidneys. The results suggest that diabetic nephropathy is caused partly by some kind of link between RAS and AGEs, so that interfering with RAS will affect production of AGEs.  Although the present finding relates to animal models, the team is now measuring AGEs in the blood of people with diabetes who take ACE inhibitors to see if their AGE levels are lower in those who do not. If ACE inhibitors prove effective in treating or preventing diabetic complications, the approval process could be hastened, since these drugs are already routinely prescribed to treat hypertension and other cardiovascular indications.

The study, funded partly by JDRF, is reported in the November issue of the journal Diabetes.  One member of the research team, Dr. Mark Cooper, Ph.D., is director of the JDRF-Danielle Alberti Memorial Center for Diabetes Complications at the Baker Heart Institute, Melbourne, Australia.

To read the abstract of this study, click below:

To read a news article about this study, click below:

To read about the Melbourne and other JDRFs Research Centers focused on the complications of diabetes, click below:

3. New Focus on Early Changes in Diabetic Retinopathy 
The cells that help maintain and protect the walls of small blood vessels are called pericytes. In people with diabetes, pericytes in the retina are commonly destroyed, with many of these people later diagnosed with diabetic retinopathy. An international team of researchers wanted to find out whether pericyte loss actually contributes to diabetic retinopathy or is merely an unrelated phenomenon. They conducted experiments with a strain of mice lacking half the gene for a growth factor, PDGF-B, which promotes pericyte recruitment to the small vessel wall during their development; as a result these animals have fewer pericytes. The researchers induced retinopathy in these pericyte-deficient mice and in normal mice to see if a shortage of pericytes led to more severe forms of the condition. They found that mice with a pericyte deficiency developed twice as many blocked blood vessels as did normal mice, suggesting that pericyte deficiency does contribute to diabetic retinopathy.!
 This raises the possibility that treatments aimed at helping pericytes survive might delay or prevent diabetic retinopathy.  The research team from six institutions in five countries includes JDRF-funded researcher, Michael Brownlee, M.D. The results were published in the October issue of the journal Diabetes.

To read the abstract of this study, click below:

Researchers at the new JDRF Center for Mechanisms and Intervention of Diabetic Retinopathy at Pennsylvania State University Hershey Medical Center, launched November 19, also are looking at certain cell types in the eye to determine their connection to retinopathy. In order for the eyes to work properly, all the cells in the retina-the neurons (impulse-conducting cells of the nervous system), the glial cells (cells that nurture and support the neurons), and the vascular (blood vessel) cells-must work together properly. In people with diabetes, these normal interactions are disturbed. The researchers are looking for ways to restore these interactions and ultimately prevent or cure the disease.

To read more about this new JDRF Center, click below:

4. Advances in Microarray Technology for Genetic Research 
Microarray technology is a powerful new research tool allowing scientists to study how large numbers of genes interact with or signal each other, and when and to what degree genes are expressed in the bodys cells.  With Microarrays (often called gene chips) - glass slides onto which DNA segments from thousands of different genes are affixed - researchers can determine the expression level of thousands of genes in a single experiment. Researchers studying type 1 diabetes are already benefiting greatly by - to cite one example - seeing which genes turn on and off in the cells of the pancreas as the organ takes shape early in life.  Such information will aid in advancing stem cell research.  A special supplement to the journal Nature Genetics analyzes the last several years of progress in this exciting field and the impact the technology has had on basic and clinical research. To read the issue, click below (available free online, registration required)

5. U.K. Releases Report on Diabetes Research Opportunities
Recently, the United Kingdoms Department of Health and the Medical Research Council released a 182-page report, "Current and Future Research on Diabetes," identifying both type 1 and type 2 research opportunities in the U.K., ranging from molecular genetics and cell biology, including stem cells, through epidemiology and prevention, to patient self-management and health services research.  The U.K. report calls for new diabetes research networks to facilitate multicenter collaborative research, especially clinical trials.  Comparable in purpose and scope to the U.S. Diabetes Research Working Group report, the report is intended to inform and influence the development of future government-sponsored (and other) diabetes research. Several JDRF-funded scientists played prominent roles in the review process and preparation of the report.

To read the report, click below:

The Juvenile Diabetes Research Foundations Research E-Newsletter provides the latest information about research on type 1 diabetes and its complications.  Please forward this report to others who may be interested.  To add your name to the distribution list, send an e-mail to email @ redacted <mailto:email @ redacted> with Subscribe to Research E-Newsletter in the subject line and your full name and postal address in the message portion of the e-mail.  If you do not wish to receive future mailings of this newsletter, please send an e-mail to email @ redacted <mailto:email @ redacted> with Unsubscribe to Research E-Newsletter in the subject line.

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