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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
>> 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 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
>> 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
>> concentrations of wheat antibodies in blood have been reported. In
>> both major
>> 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 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
>> binding to one of them, WP5212, was strongly associated with
>> pancreatic islet
>> inflammation and damage. The WP5212 putative protein has high amino
>> sequence homology with a wheat storage globulin, Glb1. Serum IgG
>> antibodies from
>> diabetic rats and humans recognized low molecular mass (33-46 kDa)
>> 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 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
>> with the autoimmune attack in the pancreas.
>> PMID: 12409286 [PubMed - in process]
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