Food-Induced Autoimmune Diabetes: Characterization of Agents and
Mechanisms
Type 1 diabetes, the most common chronic disease of childhood, is an
autoimmune disease in which the patient's own immune system attacks
and destroys the insulin-secreting beta cells in the pancreatic islets.
The susceptibility to develop diabetes is transmitted genetically and
development of overt diabetes appears to be determined by interaction
with environmental factors. Our laboratory was the first to report that
diet is a major factor determining the number of cases of diabetes that
appear in the diabetes-prone BioBreeding (BB) rat. Other laboratories
have confirmed this finding and a similar relationship was later
reported in non-obese diabetic (NOD) mice. One of the major thrusts of
our program is to identify the "diabetogenic" agents in foods.
We have partially characterized proteins from wheat and soy that may be
associated with the development of diabetes in BB rats and our data
suggest that similar findings are observed in newly diagnosed children.
We are currently screening foods to help identify relevant
diabetes-related peptides. A second focus of our laboratory is to
understand how food components or other agents encountered via the oral
route modify diabetes risk. We have found that feeding a protective diet
to susceptible animals enhances islet cell mass, decreases beta cell MHC
class I hyperexpression, and changes the Th1/Th2-Th3 cytokine balance in
the pancreas to favour Th2 (IL-10) and Th3 (TGF-beta) cytokines
(Diabetes 46:589-598, 1997). Some of the projects currently underway in
our laboratory include morphometric analysis of pancreas homeostasis,
antigenicity and determination of the natural history of Th1/Th2
cytokine balance in the pancreas and gut of diabetes-prone BB rats and
NOD mice using RT-PCR and measurement of intracellular cytokines by flow
cytometry. The aims of this work are to: provide a means of primary
prevention for type 1 diabetes, develop better diagnostic and
therapeutic agents and to understand the pathogenesis of what may be a
food-induced autoimmune disease.
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