Dipeptidyl peptidase IV inhibition enhances the intestinotrophic effect of glucagon-like peptide-2 in rats and mice

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Dipeptidyl peptidase IV inhibition enhances the intestinotrophic effect of glucagon-like peptide-2 in rats and mice. / Hartmann, B; Thulesen, J; Kissow, Hannelouise; Thulesen, S; Orskov, C; Ropke, C; Poulsen, S S; Holst, J J.

In: Endocrinology, Vol. 141, No. 11, 2000, p. 4013-20.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Hartmann, B, Thulesen, J, Kissow, H, Thulesen, S, Orskov, C, Ropke, C, Poulsen, SS & Holst, JJ 2000, 'Dipeptidyl peptidase IV inhibition enhances the intestinotrophic effect of glucagon-like peptide-2 in rats and mice', Endocrinology, vol. 141, no. 11, pp. 4013-20.

APA

Hartmann, B., Thulesen, J., Kissow, H., Thulesen, S., Orskov, C., Ropke, C., ... Holst, J. J. (2000). Dipeptidyl peptidase IV inhibition enhances the intestinotrophic effect of glucagon-like peptide-2 in rats and mice. Endocrinology, 141(11), 4013-20.

Vancouver

Hartmann B, Thulesen J, Kissow H, Thulesen S, Orskov C, Ropke C et al. Dipeptidyl peptidase IV inhibition enhances the intestinotrophic effect of glucagon-like peptide-2 in rats and mice. Endocrinology. 2000;141(11):4013-20.

Author

Hartmann, B ; Thulesen, J ; Kissow, Hannelouise ; Thulesen, S ; Orskov, C ; Ropke, C ; Poulsen, S S ; Holst, J J. / Dipeptidyl peptidase IV inhibition enhances the intestinotrophic effect of glucagon-like peptide-2 in rats and mice. In: Endocrinology. 2000 ; Vol. 141, No. 11. pp. 4013-20.

Bibtex

@article{71491de074c811dbbee902004c4f4f50,
title = "Dipeptidyl peptidase IV inhibition enhances the intestinotrophic effect of glucagon-like peptide-2 in rats and mice",
abstract = "Glucagon-like peptide-2 (GLP-2) induces intestinal growth in mice; but in normal rats, it seems less potent, possibly because of degradation of GLP-2 by the enzyme dipeptidyl peptidase IV (DPP-IV). The purpose of this study was to investigate the survival and effect of GLP-2 in rats and mice after s.c. injection of GLP-2 with or without the specific DPP-IV inhibitor, valine-pyrrolidide (VP). Rats were injected s.c. with 40 microg GLP-2 or 40 microg GLP-2+15 mg VP. Plasma was collected at different time points and analyzed, by RIA, for intact GLP-2. Rats were treated for 14 days with: saline; 15 mg VP; 40 microg GLP-2, 40 microg GLP-2+15 mg VP; 40 microg GLP-2 (3-33). Mice were treated for 10 days with: saline; 5 microg GLP-2; 5 microg GLP-2+1.5 mg VP; 25 microg GLP-2; 25 microg GLP-2 (3-33). In both cases, body weight, intestinal weight, length, and morphometric data were measured. After s.c. injection, the plasma concentration of GLP-2 reached a maximum after 15 min, and elevated concentrations persisted for 4-8 h. With VP, the concentration of intact GLP-2 was about 2-fold higher for at least the initial 60 min. Rats treated with GLP-2+VP had increased (P <0.01) small-bowel weight (4.68 +/- 0.11{\%}, relative to body weight), compared with the two control groups, [3.01 +/- 0.06{\%} (VP) and 2.94 +/- 0.07{\%} (NaCl)] and GLP-2 alone (3.52 +/- 0.10{\%}). In mice, the growth effect of 5 microg GLP-2+VP was comparable with that of 25 microg GLP-2. GLP-2 (3-33) had no effect in rats, but it had a weak effect on intestinal growth in mice. The extensive GLP-2 degradation in rats can be reduced by VP, and DPP-IV inhibition markedly enhances the intestinotrophic effect of GLP-2 in both rats and mice. We propose that DPP-IV inhibition may be considered to enhance the efficacy of GLP-2 as a therapeutic agent.",
keywords = "Animals, Body Weight, Dipeptidyl Peptidase 4, Enzyme Inhibitors, Female, Glucagon-Like Peptide 2, Glucagon-Like Peptides, Humans, Intestines, Mice, Mice, Inbred C57BL, Organ Size, Peptides, Pyrroles, Rats, Rats, Wistar, Recombinant Proteins, Valine",
author = "B Hartmann and J Thulesen and Hannelouise Kissow and S Thulesen and C Orskov and C Ropke and Poulsen, {S S} and Holst, {J J}",
year = "2000",
language = "English",
volume = "141",
pages = "4013--20",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "Oxford University Press",
number = "11",

}

RIS

TY - JOUR

T1 - Dipeptidyl peptidase IV inhibition enhances the intestinotrophic effect of glucagon-like peptide-2 in rats and mice

AU - Hartmann, B

AU - Thulesen, J

AU - Kissow, Hannelouise

AU - Thulesen, S

AU - Orskov, C

AU - Ropke, C

AU - Poulsen, S S

AU - Holst, J J

PY - 2000

Y1 - 2000

N2 - Glucagon-like peptide-2 (GLP-2) induces intestinal growth in mice; but in normal rats, it seems less potent, possibly because of degradation of GLP-2 by the enzyme dipeptidyl peptidase IV (DPP-IV). The purpose of this study was to investigate the survival and effect of GLP-2 in rats and mice after s.c. injection of GLP-2 with or without the specific DPP-IV inhibitor, valine-pyrrolidide (VP). Rats were injected s.c. with 40 microg GLP-2 or 40 microg GLP-2+15 mg VP. Plasma was collected at different time points and analyzed, by RIA, for intact GLP-2. Rats were treated for 14 days with: saline; 15 mg VP; 40 microg GLP-2, 40 microg GLP-2+15 mg VP; 40 microg GLP-2 (3-33). Mice were treated for 10 days with: saline; 5 microg GLP-2; 5 microg GLP-2+1.5 mg VP; 25 microg GLP-2; 25 microg GLP-2 (3-33). In both cases, body weight, intestinal weight, length, and morphometric data were measured. After s.c. injection, the plasma concentration of GLP-2 reached a maximum after 15 min, and elevated concentrations persisted for 4-8 h. With VP, the concentration of intact GLP-2 was about 2-fold higher for at least the initial 60 min. Rats treated with GLP-2+VP had increased (P <0.01) small-bowel weight (4.68 +/- 0.11%, relative to body weight), compared with the two control groups, [3.01 +/- 0.06% (VP) and 2.94 +/- 0.07% (NaCl)] and GLP-2 alone (3.52 +/- 0.10%). In mice, the growth effect of 5 microg GLP-2+VP was comparable with that of 25 microg GLP-2. GLP-2 (3-33) had no effect in rats, but it had a weak effect on intestinal growth in mice. The extensive GLP-2 degradation in rats can be reduced by VP, and DPP-IV inhibition markedly enhances the intestinotrophic effect of GLP-2 in both rats and mice. We propose that DPP-IV inhibition may be considered to enhance the efficacy of GLP-2 as a therapeutic agent.

AB - Glucagon-like peptide-2 (GLP-2) induces intestinal growth in mice; but in normal rats, it seems less potent, possibly because of degradation of GLP-2 by the enzyme dipeptidyl peptidase IV (DPP-IV). The purpose of this study was to investigate the survival and effect of GLP-2 in rats and mice after s.c. injection of GLP-2 with or without the specific DPP-IV inhibitor, valine-pyrrolidide (VP). Rats were injected s.c. with 40 microg GLP-2 or 40 microg GLP-2+15 mg VP. Plasma was collected at different time points and analyzed, by RIA, for intact GLP-2. Rats were treated for 14 days with: saline; 15 mg VP; 40 microg GLP-2, 40 microg GLP-2+15 mg VP; 40 microg GLP-2 (3-33). Mice were treated for 10 days with: saline; 5 microg GLP-2; 5 microg GLP-2+1.5 mg VP; 25 microg GLP-2; 25 microg GLP-2 (3-33). In both cases, body weight, intestinal weight, length, and morphometric data were measured. After s.c. injection, the plasma concentration of GLP-2 reached a maximum after 15 min, and elevated concentrations persisted for 4-8 h. With VP, the concentration of intact GLP-2 was about 2-fold higher for at least the initial 60 min. Rats treated with GLP-2+VP had increased (P <0.01) small-bowel weight (4.68 +/- 0.11%, relative to body weight), compared with the two control groups, [3.01 +/- 0.06% (VP) and 2.94 +/- 0.07% (NaCl)] and GLP-2 alone (3.52 +/- 0.10%). In mice, the growth effect of 5 microg GLP-2+VP was comparable with that of 25 microg GLP-2. GLP-2 (3-33) had no effect in rats, but it had a weak effect on intestinal growth in mice. The extensive GLP-2 degradation in rats can be reduced by VP, and DPP-IV inhibition markedly enhances the intestinotrophic effect of GLP-2 in both rats and mice. We propose that DPP-IV inhibition may be considered to enhance the efficacy of GLP-2 as a therapeutic agent.

KW - Animals

KW - Body Weight

KW - Dipeptidyl Peptidase 4

KW - Enzyme Inhibitors

KW - Female

KW - Glucagon-Like Peptide 2

KW - Glucagon-Like Peptides

KW - Humans

KW - Intestines

KW - Mice

KW - Mice, Inbred C57BL

KW - Organ Size

KW - Peptides

KW - Pyrroles

KW - Rats

KW - Rats, Wistar

KW - Recombinant Proteins

KW - Valine

M3 - Journal article

C2 - 11089531

VL - 141

SP - 4013

EP - 4020

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 11

ER -

ID: 183992