RESPONSE OF RAT IMMATURE ENTEROCYTES TO INSULIN - REGULATION BY RECEPTOR-BINDING AND ENDOLUMINAL POLYAMINE UPTAKE

Background/Aims: The mechanism(s) by which insulin stimulates enzyme expression in rat immature enterocytes are unknown. The purpose of this study was to investigate these mechanism(s). Methods: The effects of insulin or an antireceptor monoclonal antibody (RPN 538) were assessed on microvillous enzyme activities and the endoluminal uptake of [14C]spermine. Changes in de novo synthesis of polyamines were measured by mucosal ornithine decarboxylase activity. Results: In sucklings (day 14), administration of insulin failed to induce intestinal ornithine decarboxylase activity, whereas in older rats (day 18 and 20), ornithine decarboxylase was enhanced by 2-2.5-fold. Immature enterocytes from sucklings, pretreated with α-difluoromethylornithine, remained sensitive to insulin and expressed enzyme activities at levels equal to controls. In response to insulin, the uptake of [14C]spermine and the mucosal concentrations of spermine and spermidine were increased by 30%, 13%, and 39%, respectively. Administration of RPN 538 had no effect on [14C]-spermine uptake, but it prevented the effects of endogenous insulin on enzyme expression. Conclusions: The enzymatic response of immature enterocytes to insulin is mediated by binding of the hormone to its receptor and is transduced into the cell without de novo synthesis of polyamines. The regulation by insulin of the endoluminal uptake of spermine could be critical for intestinal maturation. © 1994 American Gastroenterological Association.