Dietary restriction preserves the mass and function of pancreatic beta cells via cell kinetic regulation and suppression of oxidative/ER stress in diabetic mice

作者：Kanda Yukiko^*; Hashiramoto Mitsuru; Shimoda Masashi; Hamamoto Sumiko; Tawaramoto Kazuhito; Kimura Tomohiko; Hirukawa Hidenori; Nakashima Koji; Kaku Kohei

来源：Journal of Nutritional Biochemistry, 2015, 26(3): 219-226.

DOI：10.1016/j.jnutbio.2014.10.007

• B-cell dysfunction
• Dietary restriction
• Oxidative stress
• Cell proliferation
• Cell apoptosis

To assess the molecular mechanisms by which dietary restriction preserves the beta-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, beta-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 beta-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 beta-cell function and beta-cell mass in diabetic db/db mice, suggesting that alimentary therapy prevented a-cell loss by suppressing cellular apoptosis and antioxidative stress in the pancreatic beta cells.

• 出版日期2015-3