VITAMIN-A STATUS AFFECTS THE DEVELOPMENT OF DIABETES AND INSULITIS INBB RATS

BB/Wor rats develop autoimmune diabetes mellitus with many features in common with human insulin-dependent diabetes mellitus. Since retinoid s are known to have effects on insulin secretion and immune function, these studies were designed to investigate the effects of retinoid def iciency on diabetes in BB/Wor rats and to identify a role for retinoid status in the pathogenesis of autoimmune diabetes mellitus. Litters o f diabetes-prone (DP) and diabetes-resistant (DR) BB/Wor rats were div ided at weaning and fed a diet either (1) devoid of retinoids and lead ing to clinical deficiency at approximately 60 days of age (A-def diet )-following 10 days of clinical deficiency, rats on the A-def diet wer e changed to a diet containing 2 mu g/g retinoic acid (A-def/RA diet); (2) containing 2 mu g/g retinoic acid but deficient in retinol (RA di et); or (3) replete in retinol with 4 mu g/g retinyl palmitate (RP die t). Rats receiving RP or RA diets were pair-fed to rats on the A def/R A diet. Diabetes by 120 days of age was greatly reduced (P < .01) in D P rats that received the A-def/RA diet (four of 27) or RA diet (four o f 29) versus the RP diet (13 of 31). Insulitis progressed with age in nondiabetic DP rats receiving the RP diet (P < .02) or RA diet (P < .0 5), but not the A def/RA diet (P < .22). Insulin secretion was measure d in perfused pancreas of nondiabetic rats after age 120 days and corr elated negatively with insulitis (P < .05). DP rats receiving the RP d iet had reduced insulin secretion as compared with other DP and DR rat s (P < .05), In DR rats, retinoid status had no effects on insulitis t hrough 120 days of age or on insulin secretion after 120 days of age. In conclusion, retinol deficiency reduces diabetes and insulitis in DP BB/Wor rats, and retinoic acid can at least partly substitute for ret inol in the development of insulitis. (C) 1996 by W.B. Saunders Compan y