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

Shibakami, Motonari; Shibata, Kazuhiko; Akashi, Akira; Onaka, Nobuteru; Takezaki, Jun; Tsubouchi, Gen; Yoshikawa, Hiroaki

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.

HYPOGLYCEMIC agents; POLYSACCHARIDES; BILE salts; SEQUESTRATION (Chemistry); EUGLENOIDS

Pharmaceutical Research, 2019, Vol 36, Issue 1, p1

0724-8741

Academic Journal

10.1007/s11095-018-2553-8