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.

Findings

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.

Visikol provides cutting-edge drug discovery solutions such as 3D cell culture assays and tissue imaging high content screening, AI solutions for histological analysis of tissue sections, and much more. To learn more about Visikol’s services, please contact us.

2022-11-02T09:48:08-05:00

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