4.4 Article

Oral gavage of nano-encapsulated conjugated acrylic acid-bile acid formulation in type 1 diabetes altered pharmacological profile of bile acids, and improved glycaemia and suppressed inflammation

Journal

PHARMACOLOGICAL REPORTS
Volume 72, Issue 2, Pages 368-378

Publisher

SPRINGER HEIDELBERG
DOI: 10.1007/s43440-019-00030-z

Keywords

Diabetes mellitus; Bile acid; Inflammation; Ursodeoxycholic acid; Lithocholic acid; Nanoparticles

Funding

  1. Curtin-seeding grant
  2. European Union Horizon 2020 research project and innovation program under the Marie Sklodowska-Curie Grant [872370]
  3. Australian Postgraduate Award (APA)
  4. Curtin Research Scholarship (CRS)

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Background Ursodeoxycholic acid (UDCA) is a secondary hydrophilic bile acid, metabolised in the gut, by microbiota. UDCA is currently prescribed for primary biliary cirrhosis, and of recently has shown beta-cell protective effects, which suggests potential antidiabetic effects. Thus, this study aimed to design targeted-delivery microcapsules for oral uptake of UDCA and test its effects in type 1 diabetes (T1D). Methods UDCA microcapsules were produced using alginate-NM30 matrix. Three equal groups of mice (6-7 mice per group) were gavaged daily UDCA powder, empty microcapsules and UDCA microcapsules for 7 days, then T1D was induced by alloxan injection and treatments continued until mice had to be euthanised due to weight loss > 10% or severe symptoms develop. Plasma, tissues, and faeces were collected and analysed for bile acids' concentrations. Results UDCA microcapsules brought about reduction in elevated blood glucose, reduced inflammation and altered concentrations of the primary bile acid chenodeoxycholic acid and the secondary bile acid lithocholic acid, without affecting survival rate of mice. Conclusion The findings suggest that UDCA exerted direct protective effects on pancreatic beta-cells and this is likely to be associated with alterations of concentrations of primary and secondary bile acids in plasma and tissues.

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