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Ikuko Tsukamoto,1,* Akram Hossain,2,3,* Fuminori Yamaguchi,2 Yuko Hirata,2 Youyi Dong,2 Kazuyo Kamitori,2 Li Sui,2 Machiko Nonaka,2 Masaki Ueno,4 Kazuyuki Nishimoto,5 Hirofumi Suda,5 Kenji Morimoto,6 Tsuyoshi Shimonishi,7,† Madoka Saito,8 Tao Song,9 Ryoji Konishi,1 Masaaki Tokuda2 1Department of Pharmaco-Bio-Informatics, Faculty of Medicine, Kagawa University, Miki, Kagawa, Japan; 2Department of Cell Physiology, Faculty of Medicine, Kagawa University, Kagawa, Japan; 3Matsutani Chemical Industry Co, Ltd, Itami, Japan; 4Department of Inflammation Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan; 5Division of Radioisotope Research, Life Science Research Center, Kagawa University, Kagawa, Japan; 6Rare Sugar Research Center, Kagawa University, Kagawa, Japan; 7IZUMORING LLC, Miki, Kita, Kagawa, Japan; 8Department of Pharmacy, Okayama University Hospital, Okayama, Japan; 9The First Affiliated Hospital, China Medical University, Shenyang, People’s Republic of China *These authors contributed equally to this work†Tsuyoshi Shimonishi has passed away Background: The purpose of this study was to evaluate intestinal absorption, organ distribution, and urinary elimination of the rare sugar D-psicose, a 3-carbon stereoisomer of D-fructose that is currently being investigated and which has been found to be strongly effective against hyperglycemia and hyperlipidemia. Methods: This study was performed using radioactive D-psicose, which was synthesized enzymatically from radioactive D-allose. Concentrations in whole blood, urine, and organs were measured at different time points until 2 hours after both oral and intravenous administrations and 7 days after a single oral administration (100 mg/kg body weight) to Wistar rats. Autoradiography was also performed by injecting 100 mg/kg body weight of 14C-labeled D-psicose or glucose intravenously to C3H mice. Results: Following oral administration, D-psicose easily moved to blood. The maximum blood concentration (48.5±15.6 µg/g) was observed at 1 hour. Excretion to urine was 20% within 1 hour and 33% within 2 hours. Accumulation to organs was detected only in the liver. Following intravenous administration, blood concentration was decreased with the half-life=57 minutes, and the excretion to urine was up to almost 50% within 1 hour. Similarly to the results obtained with oral administration, accumulation to organs was detected only in the liver. Seven days after the single-dose oral administration, the remaining amounts in the whole body were less than 1%. Autoradiography of mice showed results similar to those in rats. High signals of 14C-labeled D-psicose were observed in liver, kidney, and bladder. Interestingly, no accumulation of D-psicose was observed in the brain. Conclusion: D-psicose was absorbed well after oral administration and eliminated rapidly after both oral and intravenous administrations, with short duration of action. The study provides valuable pharmacokinetic data for further drug development of D-psicose. Because the findings were mainly based on animal study, it is necessary to implement human trials to study the metabolism pathway, which would give an important guide for human intake and food application of D-psicose. Keywords: 14C-labeled D-psicose, organ accumulation, pharmacokinetics, autoradiography

A calcium-based independent microbial transglutaminase treatment was used to gelatinize several suspensions and emulsions which contained commercial sodium caseinate or skim milk. The enzyme concentration employed was seen to have a marked effect on the gels produced. High enzyme concentration in caseinate gels gave steep decreases in breaking strength, strain and cohesiveness of the gels. A creep test proved that the gel made with a higher enzyme concentration was more viscoelastic. When enzymes were used in high concentrations to create skim milk gels, these showed a greater tendency to break and harden, whereas the strain and cohesiveness did not change.