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

Endocrinology. 1999 Nov;140(11):5356-63. doi: 10.1210/endo.140.11.7143.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*
  • Intestinal Mucosa / enzymology
  • Microvilli / enzymology
  • Peptide Fragments / metabolism*
  • Peptides / metabolism
  • Swine

Substances

  • Peptide Fragments
  • Peptides
  • glucagon-like peptide 1 (7-36)amide
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • Glucagon
  • Dipeptidyl Peptidase 4