Insulin-induced hepatocyte proliferation involves swelling-dependent activation of the epidermal growth factor receptor

Introduction: The aim of the study was to analyze whether the proliferative properties of insulin in rat liver do involve cross-signaling toward the epidermal growth factor receptor (EGFR), and whether this is mediated via the insulin-induced hepatocyte swelling. Methods: Perfused rat liver and primary rat hepatocytes. EGFR, c-Src and Erk phosphorylation were detected by WB, c-Src/EGFR association by EGFR IP and cell proliferation by BrdU assay. Results: In perfused rat liver, insulin (35 nmol/L) induced phosphorylation of the EGFR (Y845 and Y1173, but not at Y1045). Insulin-induced EGFR as well as Erk phosphory…