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 Apr;72(2):368-378. doi: 10.1007/s43440-019-00030-z. Epub 2020 Jan 13.

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. 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.

Keywords: Bile acid; Diabetes mellitus; Inflammation; Lithocholic acid; Nanoparticles; Ursodeoxycholic acid.

MeSH terms

  • Acrylates / chemistry
  • Acrylates / metabolism
  • Acrylates / pharmacology*
  • Animals
  • Bile Acids and Salts / blood
  • Bile Acids and Salts / metabolism*
  • Bile Acids and Salts / urine
  • Blood Glucose / metabolism*
  • Chenodeoxycholic Acid / blood
  • Chenodeoxycholic Acid / metabolism
  • Chenodeoxycholic Acid / urine
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / metabolism
  • Feces / chemistry
  • Insulin / blood
  • Lithocholic Acid / blood
  • Lithocholic Acid / metabolism
  • Lithocholic Acid / urine
  • Mice
  • Nanoconjugates / chemistry*
  • Ursodeoxycholic Acid / chemistry
  • Ursodeoxycholic Acid / metabolism
  • Ursodeoxycholic Acid / pharmacology*

Substances

  • Acrylates
  • Bile Acids and Salts
  • Blood Glucose
  • Insulin
  • Nanoconjugates
  • Chenodeoxycholic Acid
  • Lithocholic Acid
  • Ursodeoxycholic Acid
  • acrylic acid