DIETS RICH IN POLYPHENOLS AND VITAMIN A INHIBIT THE DEVELOPMENT OF TYPE I AUTOIMMUNE DIABETES IN NONOBESE DIABETIC MICE

Authors: Zunino, Susan; Storms, David; Stephensen, Charles

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/8/2007
Publication Date: 5/1/2007
Citation: Zunino, S.J., Storms, D.H., Stephensen, C.B. Diets rich in polyphenols and vitamin a inhibit the development of type i autoimmune diabetes in nonobese diabetic mice. Journal of Nutrition. 137:1216-1221.

Interpretive Summary: Type I diabetes is an autoimmune disease that is caused by immune cell destruction of the insulin-producing beta cells in the pancreas. Onset of type I diabetes usually occurs in children and young adults. Both antioxidants and vitamin A have been shown to suppress immune responses. We hypothesized that diets rich in antioxidants or vitamin A may be capable of reducing the attack on the insulin-producing beta cells and, therefore, protect against developing type I diabetes. We used nonobese diabetic mice as the model for type I diabetes. Three groups of mice were used in this study. Group 1 was fed standard control diet, group 2 was fed a diet high in vitamin A, and group 3 was fed a diet containing 1% grape powder, which has high levels of antioxidants. By approximately seven months of age, 71% of control mice became diabetic. However, only 25% of the mice fed the high vitamin A and 33% of mice fed the grape powder diet became diabetic after seven months of age. We found that the production of the inflammatory protein tumor necrosis factor alpha was significantly reduced in immune cells from mice receiving the vitamin A and grape powder diets compared to the control mice. The pancreatic tissue was examined for the presence of immune cells and there was a significant reduction of immune cells in the pancreatic tissue in mice fed the vitamin A and grape powder diets compared to the control mice. These data suggest that diets rich in antioxidants or vitamin A have protective effects against immune cell attack on the insulin-producing beta cells and these diets may have potential for reducing the onset and pathogenesis of type I diabetes.

Technical Abstract: Type I juvenile diabetes mellitus is characterized by the infiltration of activated T lymphoctes and monocytes into the islets of Langerhans of the pancreas, resulting in inflammation and progressive destruction of the insulin-producing beta 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 control diet and diets containing either 1% freeze-dried grape powder or diet supplemented with 250 IU vitamin A per gram of food. Mice were considered diabetic and euthanized when blood glucose reached 250 mg/dl or greater. By approximately seven months of age, 71% of control mice progressed to diabetes. Incidence of diabetes was 33% and 25% in mice receiving 1% dietary grape powder and vitamin A enriched diets, respectively. Isolated splenocytes from mice receiving grape powder and vitamin A supplemented diets showed a statistically significant decrease in TNF-' production after LPS stimulation. Mice receiving vitamin A-enriched diet also showed significant reduction in TNF-' levels after anti-CD3/anti-CD28 stimulation. Histological analysis of pancreatic tissue showed a significant reduction in the severity of insulitis in the mice receiving grape powder and vitamin A enriched diets compared to control mice. These data suggest that diets rich in polyphenols or vitamin A have protective effects against autoimmune inflammatory attack of the islet beta cells and may have potential for reducing the onset and pathogenesis of autoimmune diabetes.