POTENTIAL MECHANISMS BY WHICH CERTAIN FOODS PROMOTE OR INHIBIT THE DEVELOPMENT OF SPONTANEOUS DIABETES IN BB RATS - DOSE, TIMING, EARLY EFFECT ON ISLET AREA, AND SWITCH IN INFILTRATE FROM TH1 TO TH2 CELLS

Certain diets can have major effects on the development of IDDM in DP- BB rats, but data are scant on the timing, dose, and mechanisms involv ed. We therefore determined the dose response, timing, and duration of exposure required to induce diabetes, and characterized the effects o f nutritionally adequate diets with widely different diabetogenicity o n the pancreatic islet area and cytokines. DP-BB rats were fed a diabe togenic, cereal-based, NIH-07 (NIH) diet or a protective, casein or hy drolyzed casein (HC)-based, semipurified diet. Rats were fed from wean ing to 50 or 100 days with the HC diet and then switched to the NIH di et, or fed the NIH diet from weaning to 50 days and snitched to the HC diet. Pancreas histology and diabetes outcome were determined. Semiqu antitative morphometric analyses of hematoxylin and eosin-stained sect ions of pancreas from 41-day-old rats were also carried out. Diet-indu ced effects on pancreatic cytokine levels were measured at 70 days usi ng reverse transcriptase-polymerase chain reaction analysis of gamma-i nterferon (IFN-gamma), interleukin-10 (IL-10), and transforming growth factor-beta (TGF-beta). Long-term daily exposure, particularly around the beginning of puberty to late adolescence (50-100 days), was impor tant for development of diabetes. DP-BB rats could be rescued from dia betes development by feeding them a low-diabetogen HC diet as late as 50 days. Diabetes frequency was highest in rats fed 70% and 100% NIH d iets. By age 41 days, before classic insulitis, the islet area in HC-f ed DP-BB rats was 65% greater than in NIH-fed rats. By 70 days, when m ononuclear cells were visible in the islets of most NIH-fed, but not H C-fed rats.