title: Dietary restriction preserves the mass and function of pancreatic β cells via cell kinetic regulation and suppression of oxidative/ER stress in diabetic mice.
abstract: 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.
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. Electronic address: kanda@med.kawasaki-m.ac.jp.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kanda
authors.affiliation: Division of Diabetes and Endocrinology, Yodogawa Christian Hospital, Osaka, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hashiramoto
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Shimoda
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Sumiko
authors.initials: S
authors.lastname: Hamamoto
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Tawaramoto
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Hirukawa
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Nakashima
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Kaku
mesh_terms: D000818:Animals; D017209:Apoptosis; D031204:Caloric Restriction; D049109:Cell Proliferation; D048429:Cell Size; D003433:Crosses, Genetic; D056741:Cyclin D / Q000235:genetics / Q000378:metabolism; D003851:Deoxyribonucleases / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D059865:Endoplasmic Reticulum Stress; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D008297:Male; D016555:Matched-Pair Analysis; D008817:Mice, Mutant Strains; D018384:Oxidative Stress; D000075223:Poly-ADP-Ribose Binding Proteins
chemical_list: D056741:Cyclin D; D007328:Insulin; D000075223:Poly-ADP-Ribose Binding Proteins; D003851:Deoxyribonucleases; C499445:Dffb protein, mouse
keywords: Cell apoptosis; Cell proliferation; Dietary restriction; Oxidative stress; Β-cell dysfunction