Effects of chronic glucagon-like peptide-2 therapy during weaning in neonatal pigs

Sigalet, David L.; Heuvel, Elaine de; Wallace, Laurie E.; Bulloch, Estrella; Turner, Justine; Wales, Paul W.; Nation, Patrick N.; Wizzard, Pamela; Hartmann, Bolette; Assad, Meena; Holst, Jens J.

doi:10.1016/j.regpep.2013.12.006

Cited by 29 publications

(27 citation statements)

References 37 publications

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“…GLP-2 could stimulate intestinal growth by inhibiting apoptosis and increasing cell proliferation (Burrin et al, 2000). Sigalet et al (2014) found the proliferation rate of crypt cells (Ki-67 staining) increased in the GLP-2-treated animals, and the rate of apoptosis (caspase-3) decreased. However, GLP-2 (3-33) decreased the crypt Ki67-positive cells in the small intestines of dietinduced obesity models; GLP-2 also increased the per cent of caspase-3-positive cells possibly by reducing endogenous GLP-2 (Baldassano et al, 2013).…”

Section: Ki-67mentioning

confidence: 98%

“…Petersen et al (2003) found that the highest mRNA content of small intestinal GLP-2R was detected at birth; this content decreased when foetal, suckling and weaned pigs consumed enteral food; thus, enteral feeding transiently increased plasma GLP-2 concentrations and decreased the mRNA levels of small intestinal GLP-2R during the development of pigs. Similarly, the mRNA expression of GLP-2R was downregulated in various models after GLP-2 was endogenously increased with feeding or after rodent models were treated with exogenous GLP-2 (Lovshin et al, 2000;Kaji et al, 2009;Sigalet et al, 2014). The downregulation of this receptor after exposure to a receptor ligand was a common phenomenon, as in the case of epidermal growth factor receptors (Canesi et al, 2000).…”

Section: Ki-67mentioning

confidence: 99%

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PEGylated porcine glucagon-like peptide-2 improved the intestinal digestive function and prevented inflammation of weaning piglets challenged with LPS

Deng

et al. 2015

Animal

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This study was conducted to determine the effects on intestinal function, anti-inflammatory role and possible mechanism of polyethylene glycosylated (PEGylated) porcine glucagon-like peptide-2 (pGLP-2), a long-acting form of pGLP-2, in weaning piglets challenged with Escherichia coli lipopolysaccharide (LPS). We divided 18 weaned piglets on day 21 into three groups (control, LPS and LPS + PEG-pGLP-2; n = 6). The piglets from the LPS + PEG-pGLP-2 group were injected with PEG-pGLP-2 at 10 nmol/kg BW from 5 to 7 days of the trials daily. On 8 th day, the piglets in the LPS and LPS + PEG-pGLP-2 groups were intraperitoneally administered with 100 µg LPS/kg. The control group was administered with the same volume of saline solution. The piglets were then sacrificed on day 28. Afterwards, serum, duodenum, jejunum and ileum samples were collected for analysis of structural and functional endpoints. LPS + PEG-pGLP-2 treatment increased ( P < 0.05) lactase activities in the duodenum and the jejunum compared with LPS treatment. LPS + PEG-pGLP-2 treatment also significantly increased sucrase activity in the jejunum compared with LPS treatment. Furthermore, LPS treatment increased ( P < 0.05) the mRNA expression levels of interleukin (IL)-8, tumour necrosis factor-α (TNF-α) and IL-10 in the ileum compared with the control treatment. By contrast, LPS + PEG-pGLP-2 treatment decreased ( P < 0.05) the mRNA expression levels of IL-8, IL-10 and TNF-α in the ileum compared with the LPS treatment. LPS treatment also increased ( P < 0.05) the mRNA expression level of GLP-2 receptor (GLP-2R) and the percentage of GLP-2R-positive cells in the ileum; by comparison, these results were ( P < 0.05) reduced by LPS + PEG-pGLP-2 treatment. Moreover, LPS + PEGpGLP-2 treatment increased ( P < 0.05) the content of serum keratinocyte growth factor compared with the control group and the LPS group. The protective effects of PEG-pGLP-2 on intestinal digestive function were associated with the release of GLP-2R mediator (keratinocyte growth factor) and the decrease in the expressions of intestinal pro-inflammatory cytokines.

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Section: Ki-67mentioning

confidence: 98%

Section: Ki-67mentioning

confidence: 99%

PEGylated porcine glucagon-like peptide-2 improved the intestinal digestive function and prevented inflammation of weaning piglets challenged with LPS

Deng

et al. 2015

Animal

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“…Six IUGR piglets fed the RNI regimen were injected subcutaneously with GLP-2 (h[Gly2]-GLP-2, a human GLP-2 analogue; Phoenix Pharmaceuticals Inc., Belmont, CA, USA) twice daily at 0800 and 1600 h at 40 μg/kg BW per day from day 8 to day 15 postnatal as previously described (Sigalet et al, 2014). This form of GLP-2 has a longer half-life than the natural peptide due to the altered sequence and increased resistance to the proteolytic action of enzyme dipeptidyl peptidase IV.…”

Section: Methodsmentioning

confidence: 99%

Nutrient-intake-level-dependent regulation of intestinal development in newborn intrauterine growth-restricted piglets via glucagon-like peptide-2

Liu

Gao

et al. 2016

Animal

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The objective of the present study was to investigate the intestinal development of newborn intrauterine growth-restricted (IUGR) piglets subjected to normal nutrient intake (NNI) or restricted nutrient intake (RNI). Newborn normal birth weight (NBW) and IUGR piglets were allotted to NNI or RNI levels for 4 weeks from day 8 postnatal. IUGR piglets receiving NNI had similar growth performance compared with that of NBW piglets. Small intestine length and villous height were greater in IUGR piglets fed the NNI than that of piglets fed the RNI. Lactase activity was increased in piglets fed the NNI compared with piglets fed the RNI. Absorptive function, represented by active glucose transport by the Ussing chamber method and messenger RNA (mRNA) expressions of two main intestinal glucose transporters, Na + -dependent glucose transporter 1 ( SGLT1) and glucose transporter 2 ( GLUT2), were greater in IUGR piglets fed the NNI compared with piglets fed the RNI regimen. The apoptotic process, characterized by caspase-3 activity (a sign of activated apoptotic cells) and mRNA expressions of p53 (pro-apoptotic), bcl-2-like protein 4 (Bax) (pro-apoptotic) and B-cell lymphoma-2 (Bcl-2) (anti-apoptotic), were improved in IUGR piglets fed the NNI regimen. To test the hypothesis that improvements in intestinal development of IUGR piglets fed NNI might be mediated through circulating glucagon-like peptide-2 (GLP-2), GLP-2 was injected subcutaneously to IUGR piglets fed the RNI from day 8 to day 15 postnatal. Although the intestinal development of IUGR piglets fed the RNI regimen was suppressed compared with those fed the NNI regimen, an exogenous injection of GLP-2 was able to bring intestinal development to similar levels as NNI-fed IUGR piglets. Collectively, our results demonstrate that IUGR neonates that have NNI levels could improve intestinal function via the regulation of GLP-2.

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“…A study about the therapeutic application of GLP-2 in early life conducted on newborn pigs is encouraging. It showed that the exogenous administration of GLP-2 stimulates small intestinal growth during weaning in neonatal pigs without polyps or unusual growths in the intestine [56]. It is of interest to note that the authors administered a dose of 40 μg/kg/day, in two subcutaneous injections a day, which is twice that of a pharmacological dose of GLP-2 used in the majority of adult human trials [57][58][59][60].…”

Section: An Innovative Picture Of Glp-2mentioning

confidence: 99%

“…It is of interest to note that the authors administered a dose of 40 μg/kg/day, in two subcutaneous injections a day, which is twice that of a pharmacological dose of GLP-2 used in the majority of adult human trials [57][58][59][60]. They reported that the effects were limited to the gastrointestinal tract and it was well tolerated with no measurable changes in activity, growth, development, renal and hepatic function, or growth in non-gastrointestinal tissues [56]. Although this study is quite promising, the relatively short period of treatment, 42 days, should be considered and the potential side effects of prolonged treatment explored.…”

Section: An Innovative Picture Of Glp-2mentioning

confidence: 99%

GLP-2: What do we know? What are we going to discover?

Baldassano¹,

Amato²

2014

Regulatory Peptides

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The gastrointestinal tract The enteric nervous system Glucagon-like peptide 2 [GLP-2] is a 33-amino acid peptide released from the mucosal enteroendocrine L-cells of the intestine. The actions of GLP-2 are transduced by the GLP-2 receptor , which is localized in the neurons of the enteric nervous system but not in the intestinal epithelium, indicating an indirect mechanism of action. GLP-2 is well known for its trophic role within the intestine and interest in GLP-2 is now reviving based on the approval of the GLP-2R agonist for treatment of short bowel syndrome [SBS]. Recently it also seems to be involved in glucose homeostasis. The aim of this review is to outline the importance of neuroendocrine peptides, specifically of GLP-2 in the enteric modulation of the gastrointestinal function and to focus on new works in order to present an innovative picture of GLP-2.

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Effects of chronic glucagon-like peptide-2 therapy during weaning in neonatal pigs

Cited by 29 publications

References 37 publications

PEGylated porcine glucagon-like peptide-2 improved the intestinal digestive function and prevented inflammation of weaning piglets challenged with LPS

PEGylated porcine glucagon-like peptide-2 improved the intestinal digestive function and prevented inflammation of weaning piglets challenged with LPS

Nutrient-intake-level-dependent regulation of intestinal development in newborn intrauterine growth-restricted piglets via glucagon-like peptide-2

GLP-2: What do we know? What are we going to discover?

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