Intestinal absorption, organ distribution, and urinary excretion of the rare sugar D-psicose - PubMed (original) (raw)

doi: 10.2147/DDDT.S60247. eCollection 2014.

Akram Hossain 2, Fuminori Yamaguchi 3, Yuko Hirata 3, Youyi Dong 3, Kazuyo Kamitori 3, Li Sui 3, Machiko Nonaka 3, Masaki Ueno 4, Kazuyuki Nishimoto 5, Hirofumi Suda 5, Kenji Morimoto 6, Tsuyoshi Shimonishi 6, Madoka Saito 7, Tao Song 8, Ryoji Konishi 1, Masaaki Tokuda 3

Affiliations

Intestinal absorption, organ distribution, and urinary excretion of the rare sugar D-psicose

Ikuko Tsukamoto et al. Drug Des Devel Ther. 2014.

Abstract

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 (14)C-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 (14)C-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; autoradiography; organ accumulation; pharmacokinetics.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Structures and enzymatic conversion of D-glucose, D-fructose, D-psicose, and D-allose. Notes: Enzymes: a = glucose isomerase; b = D-tagatose 3 epimerase; c = L-rhamnose isomerase.

Figure 2

Figure 2

Time dependence of the blood concentration of intravenously administered D-psicose. Notes: Whole blood was collected from the femoral vein (0.1–0.2 g) and its radioactivity was measured. Radioactivity is presented as μg of D-psicose/g. The average and standard deviation from the data of 27 rats are shown. Abbreviation: IV, intravenous.

Figure 3

Figure 3

Typical autoradiograms of C3H mice. Notes: Mice were injected with 20 kBq (3 mg) of 14C-labeled glucose (n=3) (A) and 4C-labeled psicose (n=3) (B) dissolved in saline (0.2 mL) through the tail vein. Thirty minutes after injection, mice were anesthetized with diethyl ether and perfused transcardially with 0.01 M phosphate-buffered saline after cutting of the right auricle. Whole-body frozen sections (40 μm) at sagittal plane were prepared, then exposed to an imaging plate for 8 weeks. Signals of 14C-labeled psicose were observed in liver (white arrows) and urinary bladder (yellow arrows), but no signal was observed in the brain (black arrows), whereas a signal of 14C-labeled glucose was observed in the brains of all mice.

References

    1. Hossain MA, Goda F, Izuishi K, Maeta H. Protective effects of D-allose agianst ischemia-reperfusion injury of rat liver; The 1st symposium of international society of rare sugars; May 23–27; Kagawa, Japan.
    1. Cree GM, Perlin AS. O-isopropylidene derivatives of D-allulose (D-psicose) and D-erythro-hexopyranos-2,3-diulose. Can J Biochem. 1968;46:765–770. -PubMed
    1. Miller BS, Swain T. Chromatographic analysis of the free amino-acids, organic acids and sugars in wheat plant extracts. J Sci Food Agric. 1960;11:344–348.
    1. Hough L, Stacey BE. Variation in the allitol content of Itea plants during photosynthesis. Phytochemistry. 1966;5:171–175.
    1. Strecker G, Goubet B, Montreuil J. The ketoses of human urine. Identification of D (+)-allulose. C R Hebd Seances Acad Sci. 1965;260:999–1002. French. -PubMed
    2. C R Acad Sc Paris. 1965;260:999–1003. French.

MeSH terms

Substances

LinkOut - more resources