Diabetes affects approximately 37.3 million people and can lead to both short-term and long-term consequences. The most common type of diabetes is type 2, in which cells do not respond appropriately to insulin, a condition known as insulin resistance. Researchers have found that loss of insulin secretory function is caused by immune-mediated decline in beta-cell malfunction, which plays a significant role in hyperglycemia; stress adds to beta-cell immune-mediated demise during T1D progression.
Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), either alone or in combination with immunomodulators, have been recommended as a viable treatment to preserve remaining beta-cell mass. Yesildag et al., recently investigated the effects of GLP-1 RA liraglutide on beta-cell function, islet viability, and immunological activation. They found that while isolated human islets are frequently employed to research human beta-cell function in-vitro, they pose several experimental challenges. In this study, Yesildag et al., developed three in vitro islet immune injury models to provide precise functional readouts for early-stage immunopathogenesis and beta-cell dysfunction in T1D to address some of the challenges. These platforms were based on human islet microtissues (MTs), which were used to develop several T1-D-relevant islet injury platforms. In addition to human islets, the models were developed using activated peripheral blood mononuclear cells or HLA-A2 restricted preproinsulin-specific cytotoxic T lymphocytes. Islet MTs were pretreated for 24 hours with Liraglutide, extendin-4, and gliclazide, respectfully, one day before to the condition of cytokine therapy and immune cell co-cultures. Visikol® HISTO™ Penetration Buffer and Visikol® HISTO-M™ were used to perform three-dimensional confocal microscopy.
The study’s key findings include that beta-cell function was reduced in all three islet-immune damage models, as seen by elevated basal and decreased glucose-stimulated insulin release (GSIS) as well as decreased intracellular insulin levels. The loss of the first-phase insulin response (FFIR), elevated proinsulin-to-insulin ratios, HLA-class I expression, and the production of inflammatory cytokines were additional signs that T1D was progressing. [ii] By retaining FFIR and reducing immune cell infiltration and cytokine release under T1D-relevant stress, liraglutide, a glucagon-like peptide 1 receptor agonist, prevented the loss of GSIS, according to Yesildag et al.’s, in vitro study. Overall, the research of Yesildag et al., offers a paradigm for evaluating functional islet responses other than beta-cell death.
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