GLP-1 RELEASE IN MAN AFTER LOWER LARGE-BOWEL RESECTION OR INTRARECTALGLUCOSE-ADMINISTRATION

Background: This study addresses the question whether the insulinotrop ic gut hormone, glucagon-like peptide-1 (GLP-1), is released from the lower large bowel upon oral or rectal glucose uptake. Methods: It was evaluated whether rectum or sigmoid colon resection alters glucose hom eostasis or the plasma levels of the insulinotropic gut hormone, gastr ic inhibitory polypeptide (GIP), or GLP-1. Six men and 3 women (age 63 +/- 8 years, BMI 25.4 +/- 4.0 kg/m(2)) with normal preoperative fasti ng glucose values were treated before and after resection of large bow el segments. Fasting oral glucose tolerance (OGT, 75 g glucose/300 mi) tests were performed both before and 10 days postoperatively. Another approach aimed to clarify whether luminal glucose stimulation in the rectum/sigmoid colon increases GLP-1 plasma levels. Ten healthy volunt eers (4 males, 6 females, age 25 +/- 2 years, BMI 22.1 +/- 2.4 kg/m(2) ) received enemas with both saline and, 7 days later, 1 g/kg body weig ht glucose (70% glucose solution) intrarectally. Results: Neither rect um nor sigmoid colon resection led to significant changes in the pre- and postoperative glucose responses to OGT testing, or insulin, GIP an d GLP-1 release. Intrarectal glucose instillation increased blood gluc ose by about 10 mg/dl with parallel small elevations in immunoreactive insulin and immunoreactive C peptide. However, plasma GLP-1 levels re mained unaltered. Conclusion: Our data make it unlikely that GLP-1 der ived from the lower large bowel contributes significantly to maintain normal glucose tolerance.