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[IP] Pregnancy and Beyond ...Wheat Protein Pinpointed in Pioneering Diabetes Study

The text of an article in the 'Ottawa Citizen', February 5, 2003, p.1 
and 2 followed by the Journal of Biological Chemistry reference abstract.

Ottawa researcher links diet, childhood diabetes.  Wheat protein 
pinpointed in pioneering study.  by Tom Spears.

"For years the medical textbooks all agreed on one thing:  Type 1 
diabetes, the kind that strikes in childhood, is not caused by a 
person's diet.

This didn't make life easier for Fraser Scott, an Ottawa medical 
researcher looking for things in our diet that do cause the disease.  
How do you ask for funding to investigate a connection that doesn't 

This makes his team's discovery a little sweeter.  They have just 
published findings in the 'Journal of Biological Chemistry' that show a 
protein in wheat appears to cause some children's immune systems to 
attack the wrong target, damaging their body's own cells and causing 

Dr. Scott first got the idea when he worked at Health Canada in the 
early 1980s.  He was experimenting with a strain of lab mice bred to 
develop diabetes easily.  But when he put the mice on a restricted diet 
he noticed something odd.

Mouse after mouse stayed healthy, showing no signs of diabetes.

At first he suspected that someone had sold him a batch of dud mice.  
But he tried again with with more mice and got the same result.

Maybe diet is important after all he concluded.  Wheat seemed a possible 
candidate:  children with Type 1 diabetes (once called juvenile 
diabetes) often have celiac disease, an inability to digest wheat.  He 
decided to have a closer look at wheat.

Dr. Scott, Amanda MacFarlane and Karolina Burghardt at the Ottawa Health 
Research Institute and colleagues at the University of Ottawa and in 
Finland have isolated one protein in wheat that appears to cause the 
trouble.  They scanned through one million candidate proteins from 
wheat, narrowing the field first to three that caused reactions in the 
immune system, and finally one that is linked to damage in the islets, 
parts of the pancreas that produce insulin, which helps the cells break 
down sugar.  Diabetes occurs when the pancreas loses the ability to 
produce insulin.

"To put it in the simplest terms, some individuals have an abnormal 
immune system," he says.  A proper immune system should attack germs in 
our food, but not the proteins, of which we eat untold thousands, every 

But when the immune system goes off course and starts attacking the 
proteins in wheat, he suspects that it keeps going on its destructive 
course and starts attacking the insulin-producing cells in the pancreas 
as well.  Somehow he believes, wheat has mobilized these disease 
fighting cells into full-scale attack mode - but against the wrong 

These destructive cells in the immune system "are just sitting there 
until something stimulates them," Dr. Scott says.  Then they expand, 
migrate to the pancreas, and cause a long period of inflammation that 
ultimately kills the beta cell," the cell that makes insulin. Other 
infections may also play a role, possibly making this immune attack 

In his lab, one wheat protein called GlB1 caused blood from people and 
rats to "light up" in an immune reaction.  That appears to clinch the 
link with diabetes.

If his findings hold up, this will be the first protein in food shown to 
cause at least some diabetes.  (The disease also has genetic causes but 
isn't purely genetic:  If one identical twin has it, chances are only 
about 30 per cent that the other twin will have it, despite having all 
the same genes.)

The team hasn't made the type of discovery that will create new drugs.  
But they do see some uses for the findings.

It's possible they believe that exposing babies to the wheat protein at 
an early age, when the immune system is still learning what's an enemy, 
can "teach" the immune system not to react to wheat later in life.  
Another possibility is that people with family histories of diabetes may 
want to avoid wheat, "but that's a really grim diet," Dr. Scott said.

His co-author, Illimar Altossar, who teaches food biochemistry in the 
medical school at the University of Ottawa has started making "knockout" 
varieties of the wheat they used, removing just the one protein linked 
to diabetes.  He wants to see whether rats fed the knockout variety will 
still develop diabetes.

Wheat blends thousands of proteins, he said, "to make all the magical 
things we know in baking:  the dough, the aroma, the mystique of bread, 
the baguette in a bicycle pannier.  It's a very, very complex matrix."  
Looking for wheat varieties that don't have the problem protein "is the 
first thing we have to do," he also added.  Food scientists may also 
decide to engineer or breed a wheat variety without that protein.

1: J Biol Chem  2003 Jan 3;278(1):54-63

A type 1 diabetes-related protein from wheat (Triticum aestivum). cDNA 
clone of
a wheat storage globulin, Glb1, linked to islet damage.

MacFarlane AJ, Burghardt KM, Kelly J, Simell T, Simell O, Altosaar I, 
Scott FW.

Ottawa Health Research Institute, Ottawa, Ontario K1H 8L6, Canada.

The development of autoimmune type 1 diabetes involves complex 
among several genes and environmental agents. Human patients with type 1
diabetes show an unusually high frequency of wheat gluten-sensitive 
T-cell response to wheat proteins is increased in some patients, and high
concentrations of wheat antibodies in blood have been reported. In both 
models of spontaneous type 1 diabetes, the BioBreeding (BB) rat and 
diabetic mouse, at least half of the cases are diet-related. In studies 
of BB
rats fed defined semipurified diets, wheat gluten was the most potent
diabetes-inducing protein source. A major limitation in understanding 
how wheat
or other dietary antigens affect type 1 diabetes has been the difficulty 
identifying specific diabetes-related dietary proteins. To address this 
we probed a wheat cDNA expression library with polyclonal IgG antibodies 
diabetic BB rats. Three clones were identified, and the intensity of 
binding to one of them, WP5212, was strongly associated with pancreatic 
inflammation and damage. The WP5212 putative protein has high amino acid
sequence homology with a wheat storage globulin, Glb1. Serum IgG 
antibodies from
diabetic rats and humans recognized low molecular mass (33-46 kDa) wheat
proteins. Furthermore, antibodies to Glb1 protein were found in serum 
diabetic patients but not in age-, sex-, and HLA-DQ-matched controls. 
This study
raises the possibility that in some individuals, type 1 diabetes may be 
by wheat proteins. Also, it provides a first candidate wheat protein 
that is not
only antigenic in diabetic rats and human patients but is also closely 
with the autoimmune attack in the pancreas.

PMID: 12409286 [PubMed - in process]
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