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[IP] Fwd: JDRF Research E-Newsletter #29



In a message dated 02/19/2003 1:20:31 PM Pacific Standard Time,
email @ redacted writes:

> JDRF RESEARCH E-NEWSLETTER
> February 19, 2003
> No. 29
>
> 1.   Drug Blocks Pathways Leading to Complications
> 2.   Drug Blocks Diabetic Kidney Damage in Animal Studies
> 3.   Young Adults with Juvenile Diabetes at Elevated Stroke Risk
> 4.   Researchers Find Mechanism Key to Beta Cell Growth
> 5.   Autoimmune Attack on Nerve Cells Precedes Diabetes Onset
> 6.   Blood Test in Mice May Lead to Reliable Diabetes Prediction
>
> 1. Drug Blocks Pathways Leading to Complications
> With JDRF funding, a team headed by Michael Brownlee, M.D., at Albert
> Einstein
> College of Medicine in New York, and collaborators at three universities in
> Germany
> have found a drug that may prove effective against diabetes-related
> complications. In
> preliminary research, published as the featured paper in the March issue of
> the journal
> Nature Medicine, the drug, benfotiamine, a synthetic derivative of the
> dietary supplement thiamine (vitamin B1), was found to block three major
> biological mechanisms or bpathwaysb that lead to the vascular damage
> associated with eye, kidney, and nerve complications in
> diabetes.  The pathways involve (1) the formation of harmful advanced
> glycation
> endproducts (AGEs), (2) the activation of protein kinase C beta (PKC), and
> (3)
> activation of the hexosamine pathway, brought on by high blood glucose.
> When tested
> on diabetic animal models, the drug prevented the development of
> retinopathy.  As the
> first drug with the potential to block multiple major pathways leading to
> complications,
> benfotiamine could have a significant impact on a wide range of
> complications in both
> type 1 and type 2 diabetes; the drug now will have to be tested in human
> clinical trials.
>
> To read a JDRF feature story on this research, click below:
> http://www.jdrf.org/index.cfm?fuseaction=home.viewPage&
> page_id=8AC28525-1BC5-4E79-9A9079E0DE3C5739
>
> To read a USA Today story about this research, click below:
> http://www.usatoday.com/news/health/2003-02-16-diabetes_x.htm
>
> To read a press release on this research, click below:
> http://www.eurekalert.org/pub_releases/2003-02/aeco-rfp021303.php
>
> To read the abstract of this study, click below:
>
>
>
>
>
>
>
>
>
>
>
>
>
>
http://www.nature.com/cgi-taf/DynaPage.taf?file=/nm/journal/vaop/ncurrent/abs
/nm834.html
>
>
>
> 2.   Drug Blocks Diabetic Kidney Damage in Animal Studies
> A drug that already has demonstrated effectiveness in blocking progression
> of diabetic
> neuropathy (nerve damage) and retinopathy (eye disease) in human clinical
> trials now
> shows promising results in blocking nephropathy (kidney disease) as well.
> In rodents with diabetes, the drug, LY3333531, slowed kidney damage even
> though the animals had high blood glucose and high blood pressure bb two
> conditions brought on by the development of diabetes. The drug is
> classified as a "PKC inhibitor" because it inhibits an enzyme, protein
> kinase C beta (PKC), which starts a chain of events that leads to the type
> of blood vessel damage associated with nephropathy, neuropathy, and
> retinopathy. The latest study was funded by JDRF and led by Richard E.
> Gilbert, M.D. Ph.D., at the University of Melbourne, in Victoria,
> Australia. The results are reported in the February issue of the journal
> Diabetes. JDRF funded early research on PKC's role in damaging small blood
> vessels, conducted by George King, M.D. professor of medicine at Harvard
> Medical School.
>
> To read a JDRF feature story on this research, click below:
> http://www.jdrf.org/index.cfm?fuseaction=home.viewPage&
> page_id=4EDB6657-2A5E-7B6E-122C8ADDE46CD1B7
>
> To read the abstract of this study, click below:
> http://diabetes.diabetesjournals.org/cgi/content/abstract/52/2/512
>
>
> 3. Young Adults with Juvenile Diabetes at Elevated Stroke Risk
> A recent study in Britain has found that a young person with juvenile (type
> 1) diabetes has a significantly higher risk than previously thought of
> cerebrovascular diseasebbdamage to the blood vessels of the
brainbbwhich
> can lead to stroke and increased mortality. In fact, the study showed that
> among type 1 patients aged 20 to 39, the overall risk of dying from stroke
> is five-to-seven times higher than someone in the general population.
> Previous studies had documented the increased risk of stroke among people
> with type 2 diabetes, but it was not known to what extent this held true
> for people with type 1. The new research was recently published online by
> Stroke: Journal of the American Heart Association.
>
> Richard Furlanetto, M.D., Scientific Director of JDRF, said "Young people
> with type 1 diabetes and their physicians need to pay close attention to
> all heart disease risk factors, such as blood pressure and cholesterol
> levels, and intervene accordingly. They should not assume they are safe
> from these conditions that usually aren't threats for most people until
> later in life."
>
> To read a news release about this study, click below:
> http://www.sciencedaily.com/releases/2003/01/030120101058.htm
>
> To read the abstract of this study, click below:
>
>
>
>
>
http://stroke.ahajournals.org/cgi/content/abstract/01.STR.0000053843.03997.35
v1
>
>
>
> 4. Researchers Find Mechanism Key to Beta Cell Growth
> With JDRF funding, a team of researchers has identified a genetic mechanism
> by which the body promotes the growth of insulin-secreting beta cells in
> the pancreas. Knowing the mechanism presents researchers with a target for
> the development of drugs that  spur beta cell growth, possibly delaying or
> even preventing diabetes. The study was published in a recent issue of the
> Journal of  Clinical Investigation.
>
> The mechanism involves a transcription factor called Foxo1. (A
> transcription factor is a
> protein that helps control gene expression.) Normally, Foxo1 acts as a
> brake on a gene,
> Pdx1, which promotes the growth and development of beta cells. The
> researchers found that when the body needs more beta cell mass, Foxo1 is
> inhibited, so that Pdx1 is free to promote beta cell growth more strongly.
> If researchers can devise ways to inhibit Foxo1 with drugs, they might be
> able to increase beta cell mass in people with diabetes.  The increased
> mass should improve blood glucose regulation by producing more insulin.
>
> To read the full text of this study, click below:
> http://www.jci.org/cgi/content/full/110/12/1839
>
>
> 5. Autoimmune Attack On Nerve Cells Precedes Diabetes Onset
> It has always been assumed that the misguided autoimmune attack that causes
> type 1
> diabetes is aimed at pancreatic beta cellsbband nothing elsebbfrom
the
> very beginning.
> But new research suggests that the rogue immune cells first attack nervous
> system
> structures surrounding the beta cells and only subsequently shift the
> attack to beta cells.
>
> The nervous tissue being attacked is made up of Schwann cells that surround
> pancreatic islets. The researchers examined islets taken from people with
> impending type 1 diabetes and saw evidence that the Schwann cells were
> being attacked with antibodies while the islets were left alone.
>
> Also, in a study with mice prone to developing diabetes, researchers showed
> that intervening in the attack on the nervous system tissue would prevent
> the disease from developing. The finding, published in the February issue
> of the journal Nature Medicine, provides a possible new therapeutic target
> for diabetes prevention and a strategy for diagnostic tests for early
> detection of diabetes risk. It also sheds light onto a possible link
> between type 1 diabetes and autoimmune attacks on nervous tissue.
>
> The research was partly funded by JDRF, and the human islets were provided
> by the JDRF Center for Gene Therapy Approaches to Type 1 Diabetes at
> Children's Hospital of Pittsburgh and the University of Pittsburgh, led by
> Massimo Trucco, M.D.
>
> To read a news release about this study, click below:
> http://www.sickkids.on.ca/mediaroom/custom/dosch_diabetes.asp
>
> To read the abstract of this study, click below:
>
>
>
>
>
>
http://www.nature.com/cgi-taf/DynaPage.taf?file=/nm/journal/v9/n2/abs/nm818.h
tml
>
>
>
> 6. Blood Test in Mice May Lead to Reliable Diabetes Prediction
> The main barrier to detecting type 1 diabetes in its preliminary stages is
> that the immune cells responsible for this destructionbbcertain T cells
> that are bautoreactiveb
> because they react to the body's own tissuebbare very hard to measure
> because they are so few in number. Now JDRF-supported scientists report
> they have developed a way to test directly for autoreactive T cells in mice
> that are naturally prone to develop diabetes. The novel method allows the
> researchers to trap enough of the elusive autoreactive T cells to get an
> accurate count.
>
> The researchers demonstrated that this approach allowed them to predict
> with great accuracy which animals would go on to develop the disease first.
> Although the effectiveness of this method still needs to be proven in
> humans, the experiment could be an important step toward identifying
> patients at risk and gauging the effectiveness of type 1 diabetes
> treatments. The study was reported in the January 2003 issue of the Journal
> of Clinical Investigation.
>
> To read a JDRF feature story on this research, click below:
> http://www.jdrf.org/index.cfm?fuseaction=home.viewPage&
> page_id=E2A4D393-2A5E-7B6E-123F60D55F8878AE
>
> To read the full text of this study, click below:
> http://www.jci.org/cgi/content/full/111/2/217
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Date: Wed, 19 Feb 2003 15:06:36 -0500
From: email @ redacted
Subject: JDRF Research E-Newsletter #29
To: email @ redacted
Message-ID: <email @ redacted>
X-OriginalArrivalTime: 19 Feb 2003 21:18:53.0384 (UTC)
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JDRF RESEARCH E-NEWSLETTER
February 19, 2003 
No. 29

1.  Drug Blocks Pathways Leading to Complications
2.  Drug Blocks Diabetic Kidney Damage in Animal Studies
3.  Young Adults with Juvenile Diabetes at Elevated Stroke Risk 
4.  Researchers Find Mechanism Key to Beta Cell Growth
5.  Autoimmune Attack on Nerve Cells Precedes Diabetes Onset
6.  Blood Test in Mice May Lead to Reliable Diabetes Prediction

1. Drug Blocks Pathways Leading to Complications
With JDRF funding, a team headed by Michael Brownlee, M.D., at Albert Einstein 
 College of Medicine in New York, and collaborators at three universities in
Germany
 have found a drug that may prove effective against diabetes-related
complications. In
 preliminary research, published as the featured paper in the March issue of the
journal
 Nature Medicine, the drug, benfotiamine, a synthetic derivative of the dietary
supplement thiamine (vitamin B1), was found to block three major biological
mechanisms or pathways that lead to the vascular damage associated with eye,
kidney, and nerve complications in
diabetes.  The pathways involve (1) the formation of harmful advanced glycation
endproducts (AGEs), (2) the activation of protein kinase C beta (PKC), and (3)
 activation of the hexosamine pathway, brought on by high blood glucose. When
tested
 on diabetic animal models, the drug prevented the development of retinopathy.
As the
 first drug with the potential to block multiple major pathways leading to
complications,
 benfotiamine could have a significant impact on a wide range of complications
in both
 type 1 and type 2 diabetes; the drug now will have to be tested in human
clinical trials.

To read a JDRF feature story on this research, click below:

http://www.jdrf.org/index.cfm?fuseaction=home.viewPage&page_id=8AC28525-1BC5-4E79-9A9079E0DE3C5739

To read a USA Today story about this research, click below:
http://www.usatoday.com/news/health/2003-02-16-diabetes_x.htm 

To read a press release on this research, click below:
http://www.eurekalert.org/pub_releases/2003-02/aeco-rfp021303.php 

To read the abstract of this study, click below:

http://www.nature.com/cgi-taf/DynaPage.taf?file=/nm/journal/vaop/ncurrent/abs/nm834.html


2.   Drug Blocks Diabetic Kidney Damage in Animal Studies
 A drug that already has demonstrated effectiveness in blocking progression of
diabetic
 neuropathy (nerve damage) and retinopathy (eye disease) in human clinical
trials now
 shows promising results in blocking nephropathy (kidney disease) as well. In
rodents with diabetes, the drug, LY3333531, slowed kidney damage even though the
animals had high blood glucose and high blood pressure  two conditions brought
on by the development of diabetes. The drug is classified as a "PKC inhibitor"
because it inhibits an enzyme, protein kinase C beta (PKC), which starts a chain
of events that leads to the type of blood vessel damage associated with
nephropathy, neuropathy, and retinopathy. The latest study was funded by JDRF
and led by Richard E. Gilbert, M.D. Ph.D., at the University of Melbourne, in
Victoria, Australia. The results are reported in the February issue of the
journal Diabetes. JDRF funded early research on PKC's role in damaging small
blood vessels, conducted by George King, M.D. professor of medicine at Harvard
Medical School.

To read a JDRF feature story on this research, click below:

http://www.jdrf.org/index.cfm?fuseaction=home.viewPage&page_id=4EDB6657-2A5E-7B6E-122C8ADDE46CD1B7

To read the abstract of this study, click below:
http://diabetes.diabetesjournals.org/cgi/content/abstract/52/2/512    


3. Young Adults with Juvenile Diabetes at Elevated Stroke Risk  
 A recent study in Britain has found that a young person with juvenile (type 1)
diabetes has a significantly higher risk than previously thought of
cerebrovascular diseasedamage to the blood vessels of the brainwhich can
lead to stroke and increased mortality. In fact, the study showed that among
type 1 patients aged 20 to 39, the overall risk of dying from stroke is
five-to-seven times higher than someone in the general population. Previous
studies had documented the increased risk of stroke among people with type 2
diabetes, but it was not known to what extent this held true for people with
type 1. The new research was recently published online by Stroke: Journal of the
American Heart Association.
                  
 Richard Furlanetto, M.D., Scientific Director of JDRF, said "Young people with
type 1 diabetes and their physicians need to pay close attention to all heart
disease risk factors, such as blood pressure and cholesterol levels, and
intervene accordingly. They should not assume they are safe from these
conditions that usually aren't threats for most people until later in life."

To read a news release about this study, click below:
http://www.sciencedaily.com/releases/2003/01/030120101058.htm  

To read the abstract of this study, click below:
 http://stroke.ahajournals.org/cgi/content/abstract/01.STR.0000053843.03997.35v1


4. Researchers Find Mechanism Key to Beta Cell Growth
 With JDRF funding, a team of researchers has identified a genetic mechanism by
which the body promotes the growth of insulin-secreting beta cells in the
pancreas. Knowing the mechanism presents researchers with a target for the
development of drugs that spur beta cell growth, possibly delaying or even
preventing diabetes. The study was published in a recent issue of the Journal of
Clinical Investigation.

 The mechanism involves a transcription factor called Foxo1. (A transcription
factor is a
 protein that helps control gene expression.) Normally, Foxo1 acts as a brake on
a gene,
 Pdx1, which promotes the growth and development of beta cells. The researchers
found that when the body needs more beta cell mass, Foxo1 is inhibited, so that
Pdx1 is free to promote beta cell growth more strongly. If researchers can
devise ways to inhibit Foxo1 with drugs, they might be able to increase beta
cell mass in people with diabetes. The increased mass should improve blood
glucose regulation by producing more insulin.

To read the full text of this study, click below:
http://www.jci.org/cgi/content/full/110/12/1839   


5. Autoimmune Attack On Nerve Cells Precedes Diabetes Onset
 It has always been assumed that the misguided autoimmune attack that causes
type 1
 diabetes is aimed at pancreatic beta cellsand nothing elsefrom the very
beginning.
 But new research suggests that the rogue immune cells first attack nervous
system
 structures surrounding the beta cells and only subsequently shift the attack to
beta cells.

 The nervous tissue being attacked is made up of Schwann cells that surround
pancreatic islets. The researchers examined islets taken from people with
impending type 1 diabetes and saw evidence that the Schwann cells were being
attacked with antibodies while the islets were left alone.

 Also, in a study with mice prone to developing diabetes, researchers showed
that intervening in the attack on the nervous system tissue would prevent the
disease from developing. The finding, published in the February issue of the
journal Nature Medicine, provides a possible new therapeutic target for diabetes
prevention and a strategy for diagnostic tests for early detection of diabetes
risk. It also sheds light onto a possible link between type 1 diabetes and
autoimmune attacks on nervous tissue.

 The research was partly funded by JDRF, and the human islets were provided by
the JDRF Center for Gene Therapy Approaches to Type 1 Diabetes at Children's
Hospital of Pittsburgh and the University of Pittsburgh, led by Massimo Trucco,
M.D.

To read a news release about this study, click below:
http://www.sickkids.on.ca/mediaroom/custom/dosch_diabetes.asp 

To read the abstract of this study, click below:

http://www.nature.com/cgi-taf/DynaPage.taf?file=/nm/journal/v9/n2/abs/nm818.html


6. Blood Test in Mice May Lead to Reliable Diabetes Prediction
 The main barrier to detecting type 1 diabetes in its preliminary stages is that
the immune cells responsible for this destructioncertain T cells that are
autoreactive
 because they react to the body's own tissueare very hard to measure because
they are so few in number. Now JDRF-supported scientists report they have
developed a way to test directly for autoreactive T cells in mice that are
naturally prone to develop diabetes. The novel method allows the researchers to
trap enough of the elusive autoreactive T cells to get an accurate count.
                  
 The researchers demonstrated that this approach allowed them to predict with
great accuracy which animals would go on to develop the disease first. Although
the effectiveness of this method still needs to be proven in humans, the
experiment could be an important step toward identifying patients at risk and
gauging the effectiveness of type 1 diabetes treatments. The study was reported
in the January 2003 issue of the Journal of Clinical Investigation.

To read a JDRF feature story on this research, click below:

http://www.jdrf.org/index.cfm?fuseaction=home.viewPage&page_id=E2A4D393-2A5E-7B6E-123F60D55F8878AE

To read the full text of this study, click below:
http://www.jci.org/cgi/content/full/111/2/217   



 The Juvenile Diabetes Research Foundations Research E-Newsletter provides
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
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