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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

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Abstract

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 β-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 β-cells and this is likely to be associated with alterations of concentrations of primary and secondary bile acids in plasma and tissues.

Graphic abstract

Three equal groups of mice were gavaged daily UDCA (ursodeoxycholic acid) powder, empty microcapsules and UDCA microcapsules for 7 days, then T1D was induced and treatments continued until mice had to be euthanised. 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. The findings suggest that UDCA exerted direct protective effects on pancreatic β-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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Abbreviations

BAs:

Bile acids

CYP7A1:

Cholesterol-7-alphahydroxylase

FXR:

Farnesoid X receptor

T1D:

Type 1 diabetes

UDCA:

Ursodeoxycholic acid

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Acknowledgements

The authors would like to acknowledge the Australian Postgraduate Award (APA) and Curtin Research Scholarship (CRS). The authors also acknowledge the Curtin-seeding grant for the support and also acknowledge the use of laboratory equipment, scientific and technical assistance of Microscopy and Microanalysis Facility at Curtin University which has been partially funded by the University, State and Commonwealth Governments. The work is partially supported by the European Union Horizon 2020 research project and innovation program under the Marie Skłodowska-Curie Grant Agreement No 872370.

Author information

Conception and design of the project: AM, RT, GL, BK, HA-S. Analysis and interpretation of research data: AM, NZ. CI, RT, GL, MM, S G-K, HA-S. Drafting significant part of the work or critically revising it, which contributes to the interpretation: AM, NZ, CI, RT, GL, MM, SG-K, BK, HA-S. Significant contribution to data interpretation and presentation resulting in significant improvement of quality: AM, NZ, CI, HA-S. Provided data or analytical skills, which add significantly to the design, quality and readability of the work: AM, NZ, CI, HA-S.

Correspondence to Hani Al-Salami.

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Conflict of interest

Al-Salami H has been and is currently receiving of funding from Beijing Nat-Med Biotechnology Co. Ltd. The other authors have no conflict of interest to declare.

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Mooranian, A., Zamani, N., Ionescu, C.M. et al. 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. Pharmacol. Rep (2020) doi:10.1007/s43440-019-00030-z

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Keywords

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