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

• Published in: Diabetologia 1995-10, Vol.38 (10), p.1138-1147
• Main Authors: LI, X.-B, SCOTT, F. W, PARK, Y. H, YOON, J.-W
• Format: Article
• Language: English
• Subjects: Aging - immunology; Animals; Biological and medical sciences; Caseins; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - pathology; Diabetes Mellitus, Type 1 - prevention & control; Diabetes. Impaired glucose tolerance; Diet, Diabetic; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Epithelium - immunology; Esophagus - immunology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Gene Expression; Genes, MHC Class I; Histocompatibility Antigens Class I - biosynthesis; Islets of Langerhans - growth & development; Islets of Langerhans - immunology; Islets of Langerhans - pathology; Medical sciences; Pancreatic Diseases - pathology; Peripheral Nerves - immunology; Rats; Rats, Inbred BB; Species Specificity; Tongue - innervation
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/BF00422362

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.