Food ingestion induces a rapid increase in the insulinotropic glucagon-like peptide-1 (GLP-1) in plasma. Paradoxically, GLP-1 originates from the lower intestines and therefore a complex regulation of postprandial GLP-1 secretion must exist. This was addressed in the present study by utilizing an isolated vascularly perfused rat ileum preparation. Peptides and neurotransmitters thought to be candidate mediators triggering GLP-1 secretion were arterially infused and GLP-1 was measured in the venous effluent. Arterial infusion of cholinergic agonists strongly enhanced GLP-1 secretion which was counteracted by the addition of atropine. Histamine, dopamine, 5-hydoxytryptamine, gamma-aminobutyric acid, and norepinephrine had no effect. Peptides of the bombesin family were strong stimulants whereas tachykinins, enkephalins, dynorphin, TRH, calcitonin-gene-related peptide and members of the secretin family, vasoactive intestinal peptide, peptide histidine isoleucine and neuropeptide Y, were less effective. The second incretin hormone, gastric inhibitory polypeptide (GIP), was the most potent stimulant of GLP-1 secretion in our study. It enhanced GLP-1 release up to sixfold above basal during the early phase followed by a sustained secretion at 400% above basal. This stimulation remained unaffected by atropine. In conclusion, in addition to luminal stimulation of nutrients, a cholinergic impulse as well as peptidergic mediators (among them possibly GIP and GRP) may have an impact on postprandial GLP-1 secretion from the rat ileum.

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The colon contains large numbers of endocrine cells. Insight into their physiological function is limited. This is due to the fact that no sufficient model of isolated endocrine colon cells is available. In the present study we introduce an isolated vascularly perfused colon model for in vitro studies. This model offers the advantage that it keeps the endocrine cells in their physiological orientation and environment. The gut mucosa is highly sensitive to ischemia. Therefore, a careful validation of its viability is crucial in gut organ preparations. This study demonstrates that, by utilizing an oxygenated vascular medium supplemented with 25% washed bovine erythrocytes, a perfusion of the colon is achieved for at least 1 h without obvious tissue injuries. During this time parameters such as perfusion pressure, venous lactate dehydrogenase release, glucose consumption, lactate output, oxygen consumption, perfusate loss by the preparation, and morphology were analyzed. Dependent on stimulation, the endocrine L cells of the colon released glucagon-like peptide-I upon arterial perfusion of methacholine or gastrin-releasing peptide. In conclusion, a model for the isolated perfusion of the colon is introduced which is suitable for studies of endocrine colon cells.