Diets rich in polyphenols and vitamin A inhibit the development of type I autoimmune diabetes in nonobese diabetic mice

Type I juvenile diabetes mellitus is characterized by the infiltration of activated T lymphocytes and monocytes into the islets of Langerhans of the pancreas, resulting in inflammation and progressive destruction of the insulin-producing β cells. We hypothesized that feeding nonobese diabetic (NOD) mice diets rich in polyphenols or vitamin A, both known modulators of immune function, would decrease the autoimmune inflammatory process associated with type I diabetes. NOD mice were fed a control diet (C) and diets containing either 1% freeze-dried grape powder (GP) or 250 IU vitamin A/g (VA; 0.262 μmol retinyl acetate/g) of food. Mice were considered diabetic and killed when blood glucose reached 13.9 mmol/L or greater. By ∼7 mo of age, 71% of C mice progressed to diabetes. Incidence of diabetes was reduced to 33% (P < 0.05) and 25% (P < 0.05) in mice receiving 1% dietary grape powder and VA, respectively. Splenocytes from mice receiving both GP and VA had lower TNF-α production after LPS stimulation than C mice (P < 0.05). Histological analysis of pancreatic tissue showed a significant reduction in the severity of insulitis in the mice receiving GP and VA compared with C mice. These data suggest that diets rich in polyphenols or vitamin A have protective effects against autoimmune inflammatory attack of the islet β cells and have the potential to reduce the onset and pathogenesis of autoimmune diabetes.