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

Pharm Res. 2018 Dec 6;36(1):23. doi: 10.1007/s11095-018-2553-8.

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.

Keywords: GLP-1; antidiabetic agent; bile salt sequestrants; polysaccharide.

MeSH terms

  • Abdominal Fat / drug effects
  • Abdominal Fat / metabolism
  • Animals
  • Bile Acids and Salts / pharmacokinetics
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2
  • Diet, High-Fat
  • Energy Intake / drug effects
  • Feces / chemistry
  • Glucagon-Like Peptide 1 / metabolism
  • Glucans / chemistry
  • Glucans / pharmacology*
  • Hypoglycemic Agents / chemical synthesis
  • Hypoglycemic Agents / pharmacology*
  • Mice
  • Mice, Inbred C57BL

Substances

  • Bile Acids and Salts
  • Glucans
  • Hypoglycemic Agents
  • paramylon
  • Glucagon-Like Peptide 1