Oxyntomodulin stimulates intestinal glucose uptake in rats

Background and Aims: Enteroglucagon peptides have long been proposed as mediators of intestinal adaptation, including mucosal growth and nutrient absorptive capacity. The hypothesis that infusions of oxyntomodulin, a bioactive form of enteroglucagon, would stimulate glucose and amino 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 measured. At death, intestinal dimensions and brush border uptake of D-glucose and L-proline were measured using an in vitro everted sleeve technique. Results: Plasma enteroglucagon and glucagon levels were increased 4-and 12-fold, respectively, but there were no effects on food intake, body weight, or intestinal dimensions. In contrast, oxyntomodulin and glucagon significantly stimulated total intestinal glucose uptake capacity by 44% and 53%, respectively, over controls. Oxyntomodulin most potently enhanced glucose uptake in the ileum (215%), whereas glucagon's greatest effect was in the jejunum (63%-85%). However, neither 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.