CSF1R inhibition by PLX5622 affects multiple immune cell compartments with tissue-specific metabolic effects

We found that long-term CSF1R-inhibition by PLX5622 depleted tissue resident macrophages in different organs. This alteration resulted in a dual impact on glucose homeostasis with improved insulin sensitivity predominantly in the liver, combined with an insulin secretion defect in the islets of Langerhans. RNA-Seq analysis of islets of mice treated with PLX5622 compared to control mice hinted at a role of IL-1ß in supporting insulin secretion, Overall design: RNA-sequencing was performed of pancreatic islets (islets of Langerhans) from mice on PLX5622 or control diet for 5.5 or 8.5 months.