RIPK1 regulates β-cell fate via actions on gene expression and kinase signaling in a mouse model of β-cell self-reactivity.

ABSTRACT: Type 1 diabetes (T1D) is characterized by autoimmune destruction of pancreatic β-cells, insulin insufficiency, and hyperglycemia. Receptor interacting protein kinase 1 (RIPK1) is a multifunctional regulator of cell fate with kinase and scaffolding functions, and we previously identified RIPKs as regulators of β-cell cytotoxicity in vitro. Here we report that Ripk1 expression is increased in islets from aged non-obese diabetic (NOD) mice and β-cells from T1D donors, suggesting that RIPK1 may drive cytokine- and autoimmune-mediated β-cell demise in T1D. Using NIT-1 β-cells derived from NOD mice, we observed that TNFα + IFNγ increases RIPK1 phosphorylation, caspase 3/7 activity, and cell death. In contrast, this cytotoxicity was blocked with small molecule RIPK1 inhibition or in Ripk1 gene-ed

SUBMITTER: Contreras CJ 

PROVIDER: S-EPMC12920666 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature