Proinsulin stimulates growth of small intestinal crypt-like cells acting via specific receptors

Division of Nephrology, Departments of Internal Medicine I and II, University of Ulm, 89070 Ulm, Germany The mechanisms that regulate cell turnover in the intestinal epithelium are incompletely understood. Here we tested the hypothesis that proinsulin, present in serum and pancreatic juice in picomolar concentrations, stimulates growth of the rat small intestinal crypt-like cell line IEC-6 under serum-free conditions. Proinsulin binding was assessed by competitive ligand binding studies. Proinsulin and insulin-like growth factor I (IGF-I) stimulated cell proliferation up to threefold above controls, with half-maximal action already in the picomolar range and with additive effects. In early confluent cell monolayers, proinsulin bound with higher affinity (IC 50 1.3 ± 0.05 nM) and capacity (87,200 ± 2,500 receptors/cell) than IGF-I (4.0 ± 0.6; 23,700 ± 2,200, P