Dietary control of pathogenesis in C57BL/KsJ db/db diabetes mice.
Weanling C57BL/KsJ homozygous diabetic (db/db) and normal littermate (+/+ or +/db) mice were maintained for 5 mon on isocaloric diets containing either 60% sucrose, 23% casein, 8% corn oil (diet C) or 0% sucrose, 83% casein, 8% corn oil (diet B). Diabetic homozygotes consumed more diet C than normals, but ate control amounts of diet B. Diabetic mice fed diet C exhibited 57% mortality between 4 or 5 mo of age. All diabetic mutants fed the carbohydrate-free diet B appeared healthy at 6 mo of age; mutant females were normoglycemic and mutant males were only moderately hyperglycemic. Histological examination of pancreatic islets confirmed the absence of islet degeneration. In diet B maintained mutants, increased carcass fat composition, plasma and pancreatic content of insulin and glucagon, and thymidine incorporation into islets, all established that the db gene was being fully expressed. These results indicate that dietary protein stimulates islet growth and function in db/db mice, while high levels of refined carbohydrate in the diet predispose islet beta cells to undefined changes that culminate in necrosis. Restricting mutants' intake of a carbohydrate-containing diet to one-half the caloric intake of normal mice failed to block onset of beta cell necrosis. Thus, dietary composition rather than total caloric intake appears to be critical in the induction of islet necrosis and atrophy in this animal model of genetically transmitted diabetes.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics / Q000503:physiopathology*; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D004044:Dietary Proteins / Q000008:administration & dosage*; D005260:Female; D005934:Glucagon / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013936:Thymidine / Q000378:metabolism
D001786:Blood Glucose; D004040:Dietary Carbohydrates; D004044:Dietary Proteins; D007328:Insulin; D005934:Glucagon; D013936:Thymidine