Background & Aims: Enteroglucagon peptides have long been proposed as
mediators of intestinal adaptation, including mucosal growth and nutri
ent absorptive capacity. The hypothesis that infusions of oxyntomoduli
n, a bioactive form of enteroglucagon, would stimulate glucose and ami
no acid uptake was tested and its effects were compared with those of
glucagon. Methods: Rats were infused intravenously via minipumps with
either saline, rat oxyntomodulin (0.47 nmol.kg(-1).h(-1)), or glucagon
(0.88 nmol.kg(-1).h(-1)) for 7 days, and plasma hormone levels were m
easured. At death, intestinal dimensions and brush border uptake of D-
glucose and L-proline were measured using an in vitro everted sleeve t
echnique. Results: Plasma enteroglucagon and glucagon levels were incr
eased 4-and 12-fold, respectively, but there were no effects on food i
ntake, body weight, or intestinal dimensions. In contrast, oxyntomodul
in and glucagon significantly stimulated total intestinal glucose upta
ke capacity by 44% and 53%, respectively, over controls. Oxyntomodulin
most potently enhanced glucose uptake in the ileum (215%), whereas gl
ucagon's greatest effect was in the jejunum (63%-85%). However, neithe
r peptide affected proline uptake. Conclusions: These results support
a new, specific action for oxyntomodulin in intestinal adaptation as a
glucose uptake stimulator and confirm glucagon's role as a regulator
of glucose uptake.