The role of gut-glucagon-like immunoreactants in the control of gastrointestinal epithelial cell renewal.
In vitro and in vivo studies have provided considerable information on the possible physiologic function of circulating gastrointestinal hormones as well as locally acting regulatory peptides in the multifactorial control of adaptive gastrointestinal epithelial cell proliferation and cell renewal. It has been suggested by circumstantial evidences that enteroglucagon (EG; G-GLI I) may act as a trophic factor on the intestinal mucosa which may account for adaptive changes of the small intestine following various stimuli. However, we have shown that there are experimental conditions (germ-free rats after conventionalisation; jejunal self-filling blind loops) in which intestinal hyperplasia does not correspond to an increase in the concentrations of enteroglucagon in plasma or intestinal mucosa. Furthermore, despite a continuous immunoneutralisation of circulating endogenous enteroglucagon by monoclonal antibodies there was an adaptive, hyperplastic response of the ileal remnants after a 70% proximal small bowel resection which was of the same magnitude as in the control group but was even greater considering the increased number of mitoses per crypt. In order to gain additional insight into the putative role of enteroglucagon as an enterotrophic regulatory peptide, an in vitro model was used to investigate the effect of highly purified rat G-GLI I on the proliferative response of primary small intestinal epithelial cells of fetal rats. Whereas there was a well known growth-promoting action of EGF, the proliferation of rat fetal intestinal epithelial cells was inhibited by the addition of purified G-GLI I. These results indicate that enteroglucagon does not act as an enterotrophic factor but provide the first direct evidence consistent with an antitrophic role of enteroglucagon in the small intestine.
Gregor
M
M
Department of Internal Medicine, Klinikum Steglitz, Free University of Berlin.
Stallmach
A
A
Menge
H
H
Riecken
E O
EO
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D005856:Germ-Free Life; D004763:Glucagon-Like Peptides / Q000276:immunology / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology; D007421:Intestine, Small / Q000166:cytology*; D051381:Rats
D004763:Glucagon-Like Peptides