Metabolism of glucagon-like peptide-2 in pigs: Role of dipeptidyl peptidase IV

Hansen, L.; Hare, Kristine Juul; Hartmann, Bolette; Deacon, Carolyn F.; Ugleholdt, Randi; Plamboeck, Astrid; Holst, Jens J.

doi:10.1016/j.regpep.2006.08.012

Cited by 19 publications

(9 citation statements)

References 30 publications

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“…respectively). Also the native GLP2 inhibited food intake, although its action was more transient than [Gly 2 ]GLP2 and not detectable after 2 h. Excessive degradation of GLP2 catalyzed by the ubiquitous enzyme DDP-IV (Hansen et al 2007), which apparently renders the peptide inactive by N-terminal truncation, could explain the difference in the effect duration. Moreover, we have ruled out that the reduction of food intake induced by GLP2 is due to nonspecific food aversion because behavioral analysis did not show any malaise signals.…”

Section: Discussionmentioning

confidence: 97%

Food intake in lean and obese mice after peripheral administration of glucagon-like peptide 2

Baldassano¹,

Bellanca²,

Serio³

et al. 2012

Journal of Endocrinology

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We investigated the potential anorectic action of peripherally administered glucagon-like peptide 2 (GLP2) in lean and diet-induced obese (DIO) mice. Mice, fasted for 16 h, were injected i.p. with native GLP2 or [Gly 2 ]GLP2, stable analog of GLP2, before or after GLP2 (3-33), a GLP2 receptor (GLP2R) antagonist, or exendin (9-39), a GLP1R antagonist. Food intake was measured at intervals 1, 2, 4, 8, and 24 h postinjection. In addition, we tested in lean mice the influence of [Gly 2 ]GLP2 on gastric emptying and the effects of GLP1 alone or in combination with [Gly 2 ]GLP2 on food intake. [Gly 2 ]GLP2 dose dependently and significantly inhibited food intake in lean and DIO mice. The reduction of food intake occurred in the first hour postinjection and it was sustained until 4 h postinjection in lean mice while it was sustained until 2 h postinjection in DIO mice. GLP2 significantly inhibited food intake in both lean and DIO mice but only in the first hour postinjection. ]GLP2 decreased the gastric emptying rate. Results suggest that GLP2 can reduce food intake in mice in the short term, likely acting at a peripheral level. DIO mice are less sensitive to the anorectic effect of the peptide.

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Section: Discussionmentioning

confidence: 97%

Food intake in lean and obese mice after peripheral administration of glucagon-like peptide 2

Baldassano¹,

Bellanca²,

Serio³

et al. 2012

Journal of Endocrinology

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“…The intestinotrophic effect of GLP-2 is mediated by insulin-like growth factor-1 (IGF-1) derived from lamina propria myofibroblasts in the intestinal submucosa [13], which accelerates the proliferation of crypt enterocytes, increasing villus height. Stable GLP-2 analogs are usually used in these studies, since GLP-2 is rapidly degraded by dipeptidyl peptide IV (DPPIV), similar to the related hormone, insulinotropic GLP-1 [14]. DPPIV inhibition enhances the intestinotrophic action of exogenous GLP-2 [15;16].…”

Section: Introductionmentioning

confidence: 99%

Dipeptidyl Peptidase IV Inhibition Prevents the Formation and Promotes the Healing of Indomethacin-Induced Intestinal Ulcers in Rats

et al. 2013

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Backgrounds & Aims We studied the intestinotrophic hormone glucagon-like peptide-2 (GLP-2) as a possible therapy for non-steroidal anti-inflammatory drug (NSAID)-induced intestinal ulcers. Luminal nutrients release endogenous GLP-2 from enteroendocrine L cells. Since GLP-2 is degraded by dipeptidyl peptidase IV (DPPIV), we hypothesized that DPPIV inhibition combined with luminal administration of nutrients potentiates the effects of endogenous GLP-2 on intestinal injury. Methods Intestinal injury was induced by indomethacin (10 mg/kg, sc) in fed rats. The long-acting DPPIV inhibitor K579 was intragastrically (ig) or intraperitoneally (ip) given before or after indomethacin treatment. L-alanine (L-Ala) and 5′-inosine monophosphate (IMP) were co-administered ig after the treatment. Results Indomethacin treatment induced intestinal ulcers which gradually healed after treatment. Pretreatment with ig or ip K579 given either at 1 mg/kg reduced total ulcer length, whereas K579 at 3 mg/kg had no effect. Exogenous GLP-2 also reduced intestinal ulcers. The preventive effect of K579 was dose-dependently inhibited by a GLP-2 receptor antagonist. Daily treatment with K579 (1 mg/kg), GLP-2, or L-Ala + IMP after indomethacin treatment reduced total ulcer length. Co-administration (ig) of K579 and L-Ala + IMP further accelerated intestinal ulcer healing. Conclusion DPPIV inhibition and exogenous GLP-2 prevented the formation and promoted the healing of indomethacin-induced intestinal ulcers, although high-dose DPPIV inhibition reversed the preventive effect. Umami receptor agonists also enhanced the healing effects of the DPPIV inhibitor. The combination of DPPIV inhibition and luminal nutrient-induced GLP-2 release may be a useful therapeutic tool for the treatment of NSAIDs-induced intestinal ulcers.

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“…The plasma half-life of GLP-2 in the active form is estimated at approximately 7 min. Studies in pigs have shown that the metabolite of GLP-2 (3-33) is eliminated with a half-life of 22 min (6). In this study, inhibitory effects of aGLP-2 were observed at the distal ileum, where L-cells are densely localized (5).…”

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confidence: 52%

Administration of anti-glucagon-like peptide-2 serum suppresses epithelial cell proliferation of the distal small intestine in weanling rats

et al. 2009

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We investigated the effects of endogenous glucagon-like peptide-2 (GLP-2) on the development of intestinal mucosa in weanling rats. Three-week-old male weanling Sprague-Dawley rats were administered either anti-GLP-2 or normal rabbit serum every other day for 2 weeks. We then measured length, weight, and bromodeoxyuridine incorporation in the intestine on day 13 following the first injection. Administration of anti-GLP-2 serum significantly inhibited both epithelial proliferation in the distal ileum and elongation of the small intestine. These results suggest that intrinsic GLP-2 contributes to the growth of the small intestine during the weanling period.

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Metabolism of glucagon-like peptide-2 in pigs: Role of dipeptidyl peptidase IV

Cited by 19 publications

References 30 publications

Food intake in lean and obese mice after peripheral administration of glucagon-like peptide 2

Food intake in lean and obese mice after peripheral administration of glucagon-like peptide 2

Dipeptidyl Peptidase IV Inhibition Prevents the Formation and Promotes the Healing of Indomethacin-Induced Intestinal Ulcers in Rats

Administration of anti-glucagon-like peptide-2 serum suppresses epithelial cell proliferation of the distal small intestine in weanling rats

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