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Am J Physiol Endocrinol Metab 278: E134-E139, 2000;
0193-1849/00 $5.00
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Vol. 278, Issue 1, E134-E139, January 2000

Enzymatic- and renal-dependent catabolism of the intestinotropic hormone glucagon-like peptide-2 in rats

Wendy Tavares1, Daniel J. Drucker2,3, and Patricia L. Brubaker1,2

Departments of 1 Physiology and 2 Medicine, University of Toronto, Toronto, Ontario M5S 1A8; and 3 Banting and Best Diabetes Centre, Toronto Hospital, Toronto, Ontario, Canada M5G 2C4

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 [Gly2]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 [Gly2]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 [Gly2]GLP-2 were significantly reduced in nephrectomized compared with nonnephrectomized rats (P < 0.01). In contrast to both GLP-2-(1---33) and [Gly2]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.

dipeptidyl peptidase IV; kidney; clearance; degradation


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