Regulation of β-cell death by ADP-ribosylhydrolase ARH3 via lipid signaling in insulitis.

ABSTRACT:

Background

Lipids are regulators of insulitis and β-cell death in type 1 diabetes development, but the underlying mechanisms are poorly understood. Here, we investigated how the islet lipid composition and downstream signaling regulate β-cell death.

Methods

We performed lipidomics using three models of insulitis: human islets and EndoC-βH1 β cells treated with the pro-inflammatory cytokines interlukine-1β and interferon-γ, and islets from pre-diabetic non-obese mice. We also performed mass spectrometry and fluorescence imaging to determine the localization of lipids and enzyme in islets. RNAi, apoptotic assay, and qPCR were performed to determine the role of a specific factor in lipid-mediated cytokine signaling.

Results

Across all three models, lipidomic analyses sho

SUBMITTER: Sarkar S 

PROVIDER: S-EPMC10880366 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature