The pseudokinase MLKL regulates hepatic insulin sensitivity independently of inflammation.

ABSTRACT: OBJECTIVE:The mixed lineage kinase domain like (MLKL) protein, receptor interacting protein (RIPK) 1, and RIPK3 are key regulators of necroptosis, a highly pro-inflammatory mode of cell death that has been implicated in various pathological processes and human diseases. However, the role of these necroptotic regulators in diabetes remains unknown. Here we sought to delineate the role of MLKL in insulin resistance and type 2 diabetes (T2D). METHODS:We first analyzed the expression of key necroptotic regulators in obese/diabetic mouse models. We then utilized MLKL knockout (MLKL-/-) mice to evaluate the effects of MLKL on obesity-induced metabolic complications. We further determined the consequences of MLKL inhibition on hepatic insulin signaling and explored the underlying mechanism. Final

SUBMITTER: Xu H 

PROVIDER: S-EPMC6480316 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature