[acb-diabetics] enzyme may save beta cells

[Patricia LaFrance-Wolf]

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This article originally posted 31 December, 2009 and appeared in  

Issue 502

 

Relieving Stress on Insulin-producing Cells May Prevent Diabetes

 

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

(anti-oxidants). This balancing act of oxidative stress is particularly
likely to go haywire in beta cells, the insulin-producing cells that
malfunction

and then start to die off in Type 2 diabetes. 

 

Scientists at Joslin Diabetes Center now have found that a relatively
little-studied enzyme plays a central role in defending beta cells against
oxidants,

but is damaged by the high levels of blood glucose produced in diabetes. 

 

Joslin Principal Investigator Robert Stanton, M.D., who led the research,
says the discovery raises hopes of finding drugs that protect the enzyme,
and

thus the beta cells and their insulin production. Such drugs could help to
stem the tide against Type 2 diabetes, which now afflicts more than a
quarter

of a billion people worldwide. 

 

Scientists in the Stanton lab previously had found that lowered activity of
the enzyme G6PD, the main producer of an antioxidant called NAPDH, can
inflict

damage on several cell types.

 

In fact, Zhaoyun Zhang, a postdoctoral fellow and first author of the paper
was investigating G6PD activity's effect on other cell types when she made
the

initial discovery about beta cells.

 

In her earlier project, whose results were published in The FASEB Journal in
October, she was examining the diabetes-like complications that appeared in

a line of mice modified to produce less G6PD. 

 

Zhang hadn't planned to look at the pancreas, which is where the
insulin-producing beta cells are packaged together with other
hormone-producing cells in

structures called islets. 

 

But she and Chong Wee Liew, a postdoctoral fellow in the neighboring lab of
Principal Investigator Rohit Kulkarni, M.D., Ph.D., decided to take a look
at

islets in a pancreas from one of the experimental mice.

 

The islets were tiny compared to those in normal animals, suggesting
extensive damage to the beta cells. "It was very, very surprising," she
recalls. 

 

Zhang and her co-workers followed up with investigations of G6PD in beta
cells and islets, as well as studies of mice with variations in G6PD
activity (and

thus in production of the NAPDH antioxidant). 

 

"The research showed that NAPDH, an essential antioxidant upon which all
cellular antioxidants ultimately depend, can regulate the growth and death
of beta

cells," says Stanton, who also is Chief of the Nephrology Section at Joslin
Clinic and Associate Professor of Medicine at Harvard Medical School. 

 

The Joslin team went on to demonstrate that increases in the level of blood
glucose cause a decrease in NAPDH that ends up killing beta cells-and that
increasing

the level of this antioxidant guards against this effect, at least in mouse
beta cells. 

 

"Preventing the death of beta cells or stimulating beta cells to grow is a
kind of Holy Grail in diabetes prevention," Stanton notes. "Treatments aimed

at increasing this essential antioxidant hold great promise for treating or
preventing diabetes in people."

 

If this approach is successful, it could prove important for other illnesses
as well. Abnormally high level of oxidants are thought to be a major cause

of kidney disease, heart disease, hypertension, Alzheimer's disease and many
other conditions. "I hope that a new era of highly specific, targeted
treatments

will emerge that very effectively treat or possibly prevent many of these
diseases," Stanton says.

 

Published in The FASEB Journal online on Dec. 23, 2009 

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