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Rare sugar d-psicose improves insulin sensitivity and glucose tolerance in type 2 diabetes Otsuka Long-Evans Tokushima Fatty (OLETF) rats
Authors:Mohammad A Hossain  Shigeru Kitagaki  Daisuke Nakano  Akira Nishiyama  Yasunobu Funamoto  Toru Matsunaga  Ikuko Tsukamoto  Fuminori Yamaguchi  Kazuyo Kamitori  Youyi Dong  Yuko Hirata  Koji Murao  Yukiyasu Toyoda  Masaaki Tokuda
Affiliation:aDepartment of Cell Physiology, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki, Kita, Kagawa 761-0793, Japan;bSankyo Labo Service Corporation, 2-13-16, Nishi-ichinoe, Edogawa-ku, Tokyo, Japan;cDepartment of Pharmacology, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki, Kita, Kagawa 761-0793, Japan;dDepartment of Pathology, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki, Kita, Kagawa 761-0793, Japan;eDepartment of Pharmaco-Bio-Informatics, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki, Kita, Kagawa 761-0793, Japan;fDepartment of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki, Kita, Kagawa 761-0793, Japan;gDepartment of Pathobiochemistry, Faculty of Pharmacy, Meijo University, Tempaku-ku, Nagoya Aichi, Japan
Abstract:A rare sugar, d-psicose has progressively been evaluated as a unique metabolic regulator of glucose and lipid metabolism, and thus represents a promising compound for the treatment of type 2 diabetes mellitus (T2DM). The present study was undertaken to examine the underlying effector organs of d-psicose in lowering blood glucose and abdominal fat by exploiting a T2DM rat model, Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Rats were fed 5% d-psicose or 5% d-glucose supplemented in drinking water, and only water in the control for 13 weeks and the protective effects were compared. A non-diabetic Long-Evans Tokushima Otsuka (LETO), fed with water served as a counter control of OLETF. After 13 weeks feeding, d-psicose treatment significantly reduced the increase in body weight and abdominal fat mass. Oral glucose tolerance test (OGTT) showed the reduced blood glucose and insulin levels suggesting the improvement of insulin resistance in OLETF rats. Oil-red-O staining elucidated that d-psicose significantly reduced lipid accumulation in the liver. Immunohistochemical analysis showed d-psicose induced glucokinase translocation from nucleus to cytoplasm of the liver which enhances glucokinase activity and subsequent synthesis of glycogen in the liver. d-psicose also protected the pathological change of the β-cells of pancreatic islets. These data demonstrate that d-psicose controls blood glucose levels by reducing lipotoxicity in liver and by preserving pancreatic β-cell function.
Keywords:  font-variant: small-caps"  >d-psicose   Type 2 diabetes mellitus   Glucose tolerance   Insulin resistance   Glucokinase translocation   Abdominal adiposity
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