Cellular and molecular basis of intestinal and pancreatic adaptation.
This article reviews the structural and functional changes which develop in the intestine and pancreas in response to a variety of stimuli and which characterise adaptive hyper- or hypo-plasia. It then discusses the principal physiological mechanisms controlling this adaptive growth. In the gut, these include luminal nutrition, endocrine, autocrine and paracrine hormonal influences, growth factors, enterotrophic components of pancreatico-biliary secretions, neural factors, changes in blood flow and mesenchyme-epithelial interactions. The cell biology of adaptive growth involves cell membrane receptors (first messengers) and a cascade of intracellular second messengers, the best studied of which is changes in polyamine metabolism and in related enzymes. The effects of ornithine decarboxylase (ODC) blockade with difluoromethyl ornithine (DFMO) and of diamine oxidase (DAO) blockade with aminoguanidine, are described. In general, DFMO inhibits or prevents adaptive hyperplasia while in the small bowel, aminoguanidine treatment induces 'supranormal' adaptation. However, both the gut and the pancreas transport 'exogenous' (ingested in food and circulating in the blood stream) polyamines across their apical and basolateral membranes. The influence of this exogenous polyamine transport on 'endogenous' (enzyme-regulated) intracellular polyamine concentrations, is largely unknown. Finally, the molecular biology of adaptive growth is described briefly--as illustrated by the use of a growth hormone transgenic model in which mice develop marked intestinal mucosal hyperplasia and increases in the relative abundance of insulin-like growth factor-I (IGF-I) mRNA in the intestine.
Dowling
R H
RH
Gastroenterology Unit, Guy's Hospital, London, U.K.
D000222:Adaptation, Physiological; D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism; D000818:Animals; D002455:Cell Division; D006801:Humans; D006965:Hyperplasia; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology / Q000502:physiology*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D011073:Polyamines / Q000378:metabolism; D012333:RNA, Messenger
D011073:Polyamines; D012333:RNA, Messenger; D006631:Amine Oxidase (Copper-Containing)