Glucagon-like peptide-1-(7-36)amide is transformed to glucagon-like peptide-1-(9-36)amide by dipeptidyl peptidase IV in the capillaries supplying the L cells of the porcine intestine

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The insulinotropic hormone glucagon-like peptide-1 (GLP-1) is stored in the intestinal L cell in an active form, GLP-1-(7-36)amide, but more than half of the endogenous peptide circulates in an inactive, N-terminally truncated form, GLP-1-(9-36)amide. This study examined the GLP-1 newly secreted from the porcine ileum, in vitro (isolated perfused preparation) and in vivo (anesthetized pig), to determine where this conversion occurs. Although the GLP-1 extractable from the porcine ileum is predominantly the intact peptide (94.6+/-1.7%), a large proportion of the GLP-1 that is secreted has already been degraded to the truncated form both in vitro (53.8+/-0.9% intact) and in vivo (32.9+/-10.8% intact). In the presence of a specific dipeptidyl peptidase IV (DPP IV) inhibitor (valine-pyrrolidide), the proportion of intact GLP-1 released from the perfused ileum was increased under both basal (99% intact; P < 0.05) and stimulated (86-101% intact; P < 0.05) conditions. Immunohistochemical and histochemical studies revealed specific DPP IV staining in the brush border epithelium as well as in the capillary endothelium. Double staining showed juxtapositioning of DPP IV-positive capillaries and GLP-1-containing L cells. From these results, we suggest that GLP-1 is degraded as it enters the DPP IV containing blood vessels draining the intestinal mucosa.

Original languageEnglish
JournalMolecular Endocrinology
Issue number11
Pages (from-to)5356-63
Number of pages8
Publication statusPublished - Nov 1999

    Research areas

  • Animals, Capillaries/enzymology, Chromatography, High Pressure Liquid, Dipeptidyl Peptidase 4/metabolism, Endothelium, Vascular/enzymology, Epithelium/enzymology, Glucagon, Glucagon-Like Peptide 1, Glucagon-Like Peptides, Histocytochemistry, Immunohistochemistry, Intestinal Mucosa/blood supply, Microvilli/enzymology, Peptide Fragments/metabolism, Peptides/secretion, Swine

ID: 194815184