Low incidence of autoimmune type I diabetes in BB rats fed a hydrolysed casein-based diet associated with early inhibition of non-macrophage-dependent hyperexpression of MHC class I molecules on beta cells.
Diabetes-prone BioBreeding (DPBB) rats were fed a diabetogenic, mainly plant-based rodent diet, Purina Chow 5001, or a diabetes-retardant, hydrolysed casein-based diet. The expression of MHC class I antigens on pancreatic beta cells occurred at around 25 days of age in Purina Chow-fed rats, and progressively increased with the length of time of feeding with the Purina diet. Most of the Purina Chow-fed DPBB rats revealed hyperexpression of MHC class I antigens on their pancreatic beta cells by 50 days of age. Approximately 92% of the hyperexpressed Purina Chow-fed DPBB rats developed severe insulitis and diabetes. In contrast, the majority of hydrolysed casein-fed DPBB rats did not show MHC class I antigen hyperexpression and these rats failed to develop insulitis or diabetes. Purina Chow-fed Wistar-Furth rats and diabetes-resistant BioBreeding (DRBB) rats showed only very weak background staining for MHC class I antigens on their beta cells. When Purina Chow-fed (DPBB rats were treated with silica to inhibit macrophage infiltration into the pancreatic islets, the hyperexpression of MHC class I antigens was seen even more clearly, as beta cells remained intact. MHC class II antigens were not detected on pancreatic beta cells from DPBB, DRBB or Wistar-Furth rats, regardless of their diet. On the basis of these observations, we concluded that hyperexpression of MHC class I antigens on pancreatic beta cells was mainly restricted to Purina Chow-fed DPBB rats and that suppression of non-macrophage-dependent MHC class I antigen hyperexpression on pancreatic beta cells by a hydrolysed caseinbased diet resulted in the prevention of insulitis and diabetes.
Li
X B
XB
Laboratory of Viral and Immunopathogenesis of Diabetes, Julia McFarlane Diabetes Research Centre, University of Calgary Health Science Centre, Alberta, Canada.
Scott
F W
FW
Park
Y H
YH
Yoon
J W
JW
D000375:Aging / Q000276:immunology; D000818:Animals; D002364:Caseins; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D003927:Diet, Diabetic; D004848:Epithelium / Q000276:immunology; D004947:Esophagus / Q000276:immunology; D015870:Gene Expression; D005805:Genes, MHC Class I; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D007515:Islets of Langerhans / Q000254:growth & development / Q000276:immunology* / Q000473:pathology; D010182:Pancreatic Diseases / Q000473:pathology; D010525:Peripheral Nerves / Q000276:immunology; D051381:Rats; D011913:Rats, Inbred BB; D013045:Species Specificity; D014059:Tongue / Q000294:innervation
D002364:Caseins; D015395:Histocompatibility Antigens Class I