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Pharmaceutical Research

, 36:23 | Cite as

Creation of Straight-Chain Cationic Polysaccharide-Based Bile Salt Sequestrants Made from Euglenoid β-1,3-Glucan as Potential Antidiabetic Agents

  • Motonari Shibakami
  • Kazuhiko Shibata
  • Akira Akashi
  • Nobuteru Onaka
  • Jun Takezaki
  • Gen Tsubouchi
  • Hiroaki Yoshikawa
Research Paper

Abstract

Purpose

Straight-chain polysaccharides have a greater potential of selectively adsorbing hydrophobic bile salts than resin-based bile salt sequesters because of ionic and hydrophobic interactions; hence, they may possess antidiabetic activity. The feasibility of using cationic polysaccharides made from euglenoid β-1,3-glucan (referred to as paramylon) as potential antidiabetic agents was examined by using in vitro and animal experiments.

Methods

Cationic straight-chain polysaccharides were synthesized from euglenoid polysaccharide and glycidyltrimethylammonium chloride. The effects of administration of the synthetic polysaccharide on metabolic syndrome-related indicators were examined in high-fat diet-induced obesity mice. The degree of adsorption of bile salts by the polysaccharides was evaluated using spectroscopic analysis.

Results

Administration of the cationic paramylon derivatives significantly reduced body and mesenteric fat weight in high-fat diet-induced obesity mice. A noteworthy effect was that glucagon-like peptide-1 (GLP-1) secretion was approximately three times higher in diet-induced obesity mice receiving cationic paramylon derivatives than in those receiving cellulose as a control.

Conclusions

Our results indicate that these cationic paramylon derivatives are potential GLP-1 secretagogues suitable for further study.

Key Words

antidiabetic agent bile salt sequestrants GLP-1 polysaccharide 

Abbreviations

AER

Anionic exchange resin

DS

Degree of substitution

DShta

DS of the 2-hydroxy-3-(trimethylammonio)propyl group

GLP-1

Glucagon-like peptide-1

HTAP

2-hydroxy-3-(trimethylammonio)propyl paramylon

NaC

Sodium cholate

NaDC

Sodium deoxycholate

NaGC

Sodium glycocholate

NaTC

Sodium taurocholate

SEC-MALLS

Size exclusion chromatography - multi-angle laser light scattering

TG

Triglyceride

TGR5

Takeda-G protein-receptor-5

Notes

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Motonari Shibakami
    • 1
  • Kazuhiko Shibata
    • 2
  • Akira Akashi
    • 3
  • Nobuteru Onaka
    • 3
  • Jun Takezaki
    • 3
  • Gen Tsubouchi
    • 3
  • Hiroaki Yoshikawa
    • 3
  1. 1.Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST)IbarakiJapan
  2. 2.Artisan LaboYokohamaJapan
  3. 3.Technical Research CenterKOBELCO Eco-Solutions Co., Ltd.KobeJapan

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