Phosphoproteomics reveals rewiring of the insulin signaling network and multi-nodal defects in insulin resistance.

ABSTRACT: The failure of metabolic tissues to appropriately respond to insulin ("insulin resistance") is an early marker in the pathogenesis of type 2 diabetes. Protein phosphorylation is central to the adipocyte insulin response, but how adipocyte signaling networks are dysregulated upon insulin resistance is unknown. Here we employ phosphoproteomics to delineate insulin signal transduction in adipocyte cells and adipose tissue. Across a range of insults causing insulin resistance, we observe a marked rewiring of the insulin signaling network. This includes both attenuated insulin-responsive phosphorylation, and the emergence of phosphorylation uniquely insulin-regulated in insulin resistance. Identifying dysregulated phosphosites common to multiple insults reveals subnetworks containing non-canoni

SUBMITTER: Fazakerley DJ 

PROVIDER: S-EPMC9938909 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature