Antigen-specific immunotherapy combined with a regenerative drug in the treatment of experimental type 1 diabetes

Sci Rep. 2020 Nov 3;10(1):18927. doi: 10.1038/s41598-020-76041-1.

Abstract

Type 1 diabetes is an autoimmune disease caused by the destruction of the insulin-producing β-cells. To revert type 1 diabetes, the suppression of the autoimmune attack should be combined with a β-cell replacement strategy. It has been previously demonstrated that liraglutide, a glucagon-like peptide-1 receptor agonist, restores β-cell mass in type 1 diabetes, via α-cell transdifferentiation and neogenesis. We report here that treatment with liraglutide does not prevent type 1 diabetes in the spontaneous non-obese diabetic (NOD) mouse model, but it tends to reduce leukocytic islet infiltration. However, in combination with an immunotherapy based on tolerogenic liposomes, it is effective in ameliorating hyperglycaemia in diabetic NOD mice. Importantly, liraglutide is not detrimental for the tolerogenic effect that liposomes exert on dendritic cells from patients with type 1 diabetes in terms of membrane expression of molecules involved in antigen presentation, immunoregulation and activation. Moreover, the in vivo effect of the combined therapy was tested in mice humanised with peripheral blood mononuclear cells from patients with type 1 diabetes, showing no adverse effects in leukocyte subsets. In conclusion, the combination therapy with liraglutide and a liposome-based immunotherapy is a promising candidate strategy for type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Combined Modality Therapy
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / immunology
  • Female
  • Humans
  • Immunotherapy
  • Insulin / administration & dosage*
  • Insulin / chemistry
  • Insulin / pharmacology
  • Insulin-Secreting Cells / cytology*
  • Insulin-Secreting Cells / drug effects
  • Liposomes
  • Liraglutide / administration & dosage*
  • Liraglutide / pharmacology
  • Male
  • Mice
  • Mice, Inbred NOD
  • Treatment Outcome
  • Young Adult

Substances

  • Insulin
  • Liposomes
  • Liraglutide