Insulin resistance disrupts epithelial repair and niche-progenitor Fgf signaling during chronic liver injury.

ABSTRACT: Insulin provides important information to tissues about feeding behavior and energy status. Defective insulin signaling is associated with ageing, tissue dysfunction, and impaired wound healing. In the liver, insulin resistance leads to chronic damage and fibrosis, but it is unclear how tissue-repair mechanisms integrate insulin signals to coordinate an appropriate injury response or how they are affected by insulin resistance. In this study, we demonstrate that insulin resistance impairs local cellular crosstalk between the fibrotic stroma and bipotent adult liver progenitor cells (LPCs), whose paracrine interactions promote epithelial repair and tissue remodeling. Using insulin-resistant mice deficient for insulin receptor substrate 2 (Irs2), we highlight dramatic impairment of proregene

SUBMITTER: Manzano-Nunez F 

PROVIDER: S-EPMC6368328 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature