Effects of oxyntomodulin on intestinal adaptation in the rat



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Texas Tech University


Enteroglucagon (EG) has long been suggested to be an enterotrophic (mucosal growth) factor based on circumstantial evidence. This study evaluated the effects of/«- vivo infusions of synthetic rat oxyntomodulin (OXN, a bioactive form of EG) and glucagon on intestinal adaptation in rats. Osmotic minipumps which deliver peptides or saline intravenously for up to two weeks were implanted into rats fed with either lab chow or a carbohydrate-free diet. At sacrifice, the entire small intestine was removed, and glucose and proline uptake across the brush border was measured using the everted sleeve method. Gut morphology was also measured to assess effects on growth. Surprisingly, OXN infusion had no effect on intestinal growth, despite the putative correlation between EG and enterocyte proliferation. In contrast, infusion of OXN increased active glucose uptake by 13-48% in proximal gut, and by nearly 300% in the ileum. However, OXN showed no effect on proline uptake. On the other hand, glucagon infusion increased active glucose uptake by 100-150% in the proximal and middle part of the intestine, but only showed modest effect on the distal gut. Similarly, glucagon infusion had no effects on proline uptake or intestinal growth. These results were affected by diet since rats fed with lab chow and infused with lower dose of OXN showed no effects. This study demonstrates for the first time that OXN or glucagon increases intestinal nutrient absorption by specifically stimulating glucose uptake. These results do not support the long-standing hypothesis of OXN as a gut growth factor.



Intestines, Glucagon, Rats