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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 
>> exist?
>> 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 
>> diabetes.
>> 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 day."
>> 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 target.
>> 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 
>> worse.
>> 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 
>> interactions
>> among several genes and environmental agents. Human patients with 
>> type 1
>> diabetes show an unusually high frequency of wheat gluten-sensitive 
>> enteropathy;
>> T-cell response to wheat proteins is increased in some patients, and 
>> high
>> concentrations of wheat antibodies in blood have been reported. In 
>> both major
>> models of spontaneous type 1 diabetes, the BioBreeding (BB) rat and 
>> non-obese
>> 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 in
>> identifying specific diabetes-related dietary proteins. To address 
>> this issue,
>> we probed a wheat cDNA expression library with polyclonal IgG 
>> antibodies from
>> diabetic BB rats. Three clones were identified, and the intensity of 
>> antibody
>> binding to one of them, WP5212, was strongly associated with 
>> pancreatic islet
>> 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 
>> from
>> 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 induced
>> 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 
>> linked
>> with the autoimmune attack in the pancreas.
>> PMID: 12409286 [PubMed - in process]
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