Enzymatic- and renal-dependent catabolism of the intestinotropic hormone glucagon-like peptide-2 in rats.
The intestinotropic hormone glucagon-like peptide (GLP)-2-(1-33) is cleaved in vitro to GLP-2-(3-33) by dipeptidyl peptidase IV (DP IV). To determine the importance of DP IV versus renal clearance in the regulation of circulating GLP-2-(1-33) levels in vivo, GLP-2-(1-33) or the DP IV-resistant analog [Gly(2)]GLP-2 was injected in normal or DP IV-negative rats and assayed by HPLC and RIA. Normal rats showed a steady degradation of GLP-2-(1-33) to GLP-2-(3-33) over time, whereas little or no conversion was detected for GLP-2-(1-33) in DP IV-negative rats and for [Gly(2)]GLP-2 in normal rats. To determine the role of the kidney in clearance of GLP-2-(1-33) from the circulation, normal rats were bilaterally nephrectomized, and plasma immunoreactive GLP-2 levels were measured. The slope of the disappearance curves for both GLP-2-(1-33) and [Gly(2)]GLP-2 were significantly reduced in nephrectomized compared with non-nephrectomized rats (P < 0.01). In contrast to both GLP-2-(1-33) and [Gly(2)]GLP-2, GLP-2-(3-33) did not stimulate intestinal growth in a murine assay in vivo. Thus the intestinotropic actions of GLP-2-(1-33) are determined both by the actions of DP IV and by the kidney in vivo in the rat.
Tavares
W
W
Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8.
Drucker
D J
DJ
Brubaker
P L
PL
D000595:Amino Acid Sequence; D000818:Animals; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D036341:Intercellular Signaling Peptides and Proteins; D007422:Intestines / Q000254:growth & development*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009392:Nephrectomy; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D012016:Reference Values
C117499:(glycyl-glycyl)GLP-2; D053767:Glucagon-Like Peptide 2; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D010455:Peptides; D004763:Glucagon-Like Peptides; D018819:Dipeptidyl Peptidase 4