In:
The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 85, No. 8 ( 2000-08-01), p. 2884-2888
Abstract:
Glucagon-like peptide-2 (GLP-2), an intestinal product of glucagon gene expression which induces intestinal growth in mice, has been proposed as a treatment for intestinal insufficiency. GLP-2 is metabolized extensively by dipeptidyl peptidase IV (DPP-IV) in rats, but less is known about its fate in humans. Therefore, GLP-2 metabolism was investigated in healthy volunteers after 1) a 500-Cal mixed meal (n = 6), 2) iv infusion of synthetic human GLP-2 (0.8 pmol/kg·min; n = 8), 3) a sc bolus injection (400 μg; n = 9), and 4) in vitro incubation in plasma and blood (1000 pmol/L; n = 4). GLP-2 concentrations were determined by N-terminal RIA measuring only intact GLP-2, side-viewing RIA measuring intact and degraded forms [e.g. GLP-2-(3–33) arising from DPP-IV degradation], and high performance liquid chromatography (HPLC). Meal ingestion elevated plasma GLP-2 (intact, 16 ± 3 to 73 ± 10 pmol/L at 90 min), and HPLC revealed two immunoreactive components: intact GLP-2 (57 ± 2%) and GLP-2-(3–33). GLP-2 infusion increased plasma levels [intact, 9 ± 4 to 131 ± 11 pmol/L; total, 23 ± 7 to 350 ± 18 pmol/L; the differences represent GLP-2-(3–33)] . The elimination t1/2 values were 7.2 ± 2 min (intact GLP-2) and 27.4 ± 5.4 min[ GLP-2-(3–33)], and MCRs were 6.8 ± 0.6 and 1.9 ± 0.3 mL/kg·min, respectively. Subcutaneous injection increased intact GLP-2 to maximally 1493 ± 250 pmol/L at 45 min, whereas total GLP-2 increased to 2793 ± 477 pmol/L at 90 min. At 60 min, plasma contained 69 ± 1% intact GLP-2. In vitro the t1/2 values were 8.0 ± 1.5 h (plasma) and 3.3 ± 0.3 h (blood). GLP-2-(3–33) was the only degradation product identified by HPLC, and a DPP-IV inhibitor abolished the degradation of GLP-2 in vitro. We conclude that GLP-2 is extensively degraded to GLP-2-(3–33) in humans, presumably by DPP-IV. Nevertheless, 69% remains intact 1 h after GLP-2 injection, supporting the possibility of sc use in patients with intestinal insufficiency.
Type of Medium:
Online Resource
ISSN:
0021-972X
,
1945-7197
DOI:
10.1210/jcem.85.8.6717
Language:
English
Publisher:
The Endocrine Society
Publication Date:
2000
detail.hit.zdb_id:
2026217-6
Permalink