Dietary Restriction Preserves the Mass and Function of Pancreatic β Cells Via Cell Kinetic Regulation and Suppression of Oxidative/ER Stress in Diabetic Mice

To assess the molecular mechanisms by which dietary restriction preserves the β-cell mass and function in diabetic db/db mice. Male db/db mice were divided into two groups with or without diet restriction. Daily food intake of db/db mice was adjusted to that of the control db/m mice, which was determined in advance. A dietary restriction was implemented for 6 weeks from 6 weeks of age. Islet morphology, β-cell function and gene expression profiles specific for pancreatic islet cells were compared. Food intake in db/m mice was 50% of that in db/db mice. Impaired glucose tolerance and insulin sensitivity were significantly ameliorated in db/db mice with dietary restriction. The pancreatic β-cell mass was greater in mice with dietary restriction than that in mice without intervention. The dietary restriction significantly increased cyclin D gene expression and down-regulated CAD gene expression at 12 weeks compared with untreated db/db mice. Antiapoptotic bcl-2 gene expression was significantly increased, whereas genes related to oxidative stress, ER stress and inflammatory processes, such as NADPH oxidase, CHOP10 and TNF, were markedly down-regulated in mice with dietary restriction. Dietary restriction preserved the pancreatic β-cell function and β-cell mass in diabetic db/db mice, suggesting that alimentary therapy prevented β-cell loss by suppressing cellular apoptosis and antioxidative stress in the pancreatic β cells.