Liraglutide protects β-cells in novel human islet spheroid models of type 1 diabetes

Clin Immunol. 2022 Nov:244:109118. doi: 10.1016/j.clim.2022.109118. Epub 2022 Sep 6.


To enable accurate, high-throughput and longer-term studies of the immunopathogenesis of type 1 diabetes (T1D), we established three in-vitro islet-immune injury models by culturing spheroids derived from primary human islets with proinflammatory cytokines, activated peripheral blood mononuclear cells or HLA-A2-restricted preproinsulin-specific cytotoxic T lymphocytes. In all models, β-cell function declined as manifested by increased basal and decreased glucose-stimulated insulin release (GSIS), and decreased intracellular insulin content. Additional hallmarks of T1D progression such as loss of the first-phase insulin response (FFIR), increased proinsulin-to-insulin ratios, HLA-class I expression, and inflammatory cytokine release were also observed. Using these models, we show that liraglutide, a glucagon-like peptide 1 receptor agonist, prevented loss of GSIS under T1D-relevant stress, by preserving the FFIR and decreasing immune cell infiltration and cytokine secretion. Our results corroborate that liraglutide mediates an anti-inflammatory effect that aids in protecting β-cells from the immune-mediated attack that leads to T1D.

Keywords: Insulin secretion; Liraglutide; Pancreatic beta cell; Pseudoislets; Type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Cytokines / metabolism
  • Diabetes Mellitus, Type 1* / metabolism
  • Glucose / metabolism
  • HLA-A2 Antigen
  • Humans
  • Insulin
  • Insulin-Secreting Cells* / metabolism
  • Islets of Langerhans*
  • Leukocytes, Mononuclear / metabolism
  • Liraglutide / metabolism
  • Liraglutide / pharmacology
  • Proinsulin / metabolism


  • Anti-Inflammatory Agents
  • Cytokines
  • HLA-A2 Antigen
  • Insulin
  • Liraglutide
  • Proinsulin
  • Glucose