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 Intestine¹

TLDR

GLP‑1 is stored in intestinal L cells as the active GLP‑1‑(7–36)amide, yet more than half of the peptide circulates as the inactive truncated GLP‑1‑(9–36)amide. The study aimed to identify the site of GLP‑1 conversion in the porcine ileum. Researchers examined GLP‑1 secretion in isolated perfused ileum and anesthetized pigs to determine where the conversion occurs. They found that most secreted GLP‑1 is already truncated, that a DPP‑IV inhibitor restores intact GLP‑1, and that DPP‑IV is localized to capillary endothelium adjacent to L cells, indicating degradation occurs as GLP‑1 enters DPP‑IV–containing vessels.

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.