OXYNTOMODULIN STIMULATES INTESTINAL GLUCOSE-UPTAKE IN RATS

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.