[acb-diabetics] new enzyme may cause beta cell destruction

[Patricia LaFrance-Wolf]

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This article originally posted 11 January, 2010 and appeared in
<http://www.diabetesincontrol.com/diabetes-in-control-newsletters/504> Issue
504,
<http://www.diabetesincontrol.com/topics/complications-and-co-morbidities>
Complications and Co-morbidities 

 



Joslin Identifies Source of Beta Cell Damage


Scientists at the Joslin Diabetes Center, Boston, MA, led by Principal
Investigator Robert Stanton, M.D., have discovered that high blood glucose
levels damage a key enzyme that guards insulin-producing beta cells. Their
surprising finding raises hopes of finding drugs that protect the enzyme,
and thus the beta cells and their insulin production. The discovery focuses
on a cellular process known as "oxidative stress."


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Dr. Stanton explains that cells in your body are constantly churning out
poisonous forms of oxygen (oxidants) and mopping them up with a
countervailing force of proteins and chemicals (antioxidants). This
balancing act of oxidative stress is particularly likely to go haywire in
beta cells, which malfunction and then start to die off in people with
diabetes. 

Scientists in the Stanton lab previously showed that lowered activity of a
relatively little-studied enzyme called G6PD, which is the main producer of
an antioxidant called NAPDH, can inflict damage on several other types of
cells. 

While studying mice modified to produce less G6PD, and thus NAPDH,
postdoctoral fellow Zhaoyun Zhang found herself wondering about the effects
on the pancreas, which is where beta cells are found in structures called
islets. 

Not an expert on beta cells, she talked with Chong Wee Liew, a postdoctoral
fellow studying beta cells in the neighboring lab of Principal Investigator
Rohit Kulkarni, M.D., Ph.D. ("That's the advantage of working at Joslin,"
she remarks. "There are so many people you can talk to who have so much
expertise.")

The two researchers looked at a pancreas from one of the experimental mice,
with startling results. Its islets were tiny compared to those in normal
animals -- suggesting that the beta cells had been extensively damaged.

In follow-up research, Dr. Zhang and her colleagues showed that NAPDH can
regulate the growth and death of beta cells. The Joslin team went on to
demonstrate that increases in blood glucose levels cause a decrease in NAPDH
that ends up killing beta cells -- and that boosting production of this key
antioxidant guards against the damage, at least in mouse beta cells. 

"This research discovery, which identifies a key enzyme that regulates
oxidation and pancreatic cell death, brings us closer than ever to getting
at the root of diabetes," comments Gerald Weissmann, M.D., Editor-in-Chief
of the FASEB Journal.

"Preventing the death of beta cells or stimulating beta cells to grow is a
Holy Grail in diabetes prevention," says Dr. Stanton. "Treatments aimed at
increasing this essential antioxidant hold great promise for treating or
preventing diabetes."

With Dr. Stanton's guidance, his research team has begun to study drugs that
are promising candidates for guarding against damage to beta cells. 

 

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