Inhibition of RIPK1 kinase does not affect diabetes development: β-Cells survive RIPK1 activation

• DOI: 10.1016/j.molmet.2023.101681
• Publication Date: 2023-01-24T07:26:13Z
• Authors: Tatiana Takiishi; Peng Xiao; Marie Franchimont; Eduardo H. Gilglioni; Erick N. Arroba; Esteban N. Gurzov; Mathieu JM. Bertrand; Alessandra K. Car...
• Keywords: RIPK1

Type 1 diabetes (T1D) is caused by progressive immune-mediated loss of insulin-producing β-cells. Inflammation detrimental to β-cell function and survival, moreover, both apoptosis necrosis have been implicated as mechanisms in T1D. The receptor interacting serine/threonine protein kinase (RIPK1) promotes inflammation serving a scaffold for NF-κB MAPK activation, or acting that triggers necroptosis. It unclear whether RIPK1 activity involved T1D pathology. In the present study, we investigated if absence activation would affect susceptibility diet induced obesity (DIO). knockin mouse line carrying mutation mimicking serine 25 phosphorylation (Ripk1S25D/S25D), which abrogates activity, was utilized assess vivo role vitro, death analysed conditions known induce RIPK1-dependent apoptosis/necroptosis. We demonstrate Ripk1S25D/S25D mice presented normal glucose metabolism function. Furthermore, DIO were not different between Ripk1+/+ mice. Despite strong other necroptosis effectors (RIPK3 MLKL) TNF+BV6+zVAD, no cell observed islets nor human Our results contrast recent literature showing most types undergo following activation. This peculiarity may reflect an adaptation inability β-cells proliferate self-renewal.