The role of polyamines in glucagon-like peptide-2 prevention of TPN-induced gut hypoplasia

Chance, William T.; Sheriff, Sulaiman; Dayal, Ramesh; Friend, Lou Ann; Thomas, Ingrid; Balasubramaniam, Ambikaipakan

doi:10.1016/j.peptides.2005.09.012

Cited by 6 publications

(5 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PCNA is an auxiliary protein of DNA polymerase-δ that plays a role in both DNA replication and repair [25]. Our results demonstrate that GLP-2 induces a strong increase in PCNA in cultured astrocytes, which is consistent with the findings on crypt cell proliferation rate in mice [26,27] but unlike that reported for the jejunal mucosa of total parenteral-nutrition-maintained rats [28]. Expression of the astrocyte-specific marker GFAP is regulated by several hormones and growth factors, but the protein is also expressed in response to inflammation [29].…”

Section: Discussionsupporting

confidence: 91%

Synergistic Effect of Glucagon-Like Peptide 2 (GLP-2) and of Key Growth Factors on the Proliferation of Cultured Rat Astrocytes. Evidence for Reciprocal Upregulation of the mRNAs for GLP-2 and IGF-I Receptors

2009

View full text Add to dashboard Cite

The aim of this work was to determine whether the stimulating effect of glucagon-like peptide (GLP)-2 on astrocyte proliferation could be reinforced by proliferating substances, including growth factors such as EGF, platelet-derived growth factor, insulin-like growth factor type I (IGF-I) or a hormone such as insulin. Both DNA synthesis and astrocyte density, as well as the expression of c-Fos, Ki-67, proliferating cell nuclear antigen and glial fibrillary acidic proteins, were found to be higher in the presence of GLP-2 than in its absence. In an attempt to get a better understanding of this process, intracellular cyclic adenosine monophosphate (cAMP) production, extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and the expression of GLP-2R and IGF-I receptor (IGF-IR) mRNAs were studied in response to growth factors. Our results indicate that, in the presence of different growth factors, GLP-2 does not increase cAMP production but raises ERK 1/2 phosphorylation. In addition, GLP-2R mRNA expression was increased by IGF-I, whilst mRNA expression of IGF-IR was higher in cells incubated with GLP-2 than in control cells. These results suggest for the first time that GLP-2 and several growth factors show synergistic effects on the proliferation of rat astrocytes, a process in which an enhanced expression of GLP-2R and IGF-IR may be involved, providing additional insights into the physiological role of this novel neuropeptide, specially during astroglial regeneration.

show abstract

Section: Discussionsupporting

confidence: 91%

Synergistic Effect of Glucagon-Like Peptide 2 (GLP-2) and of Key Growth Factors on the Proliferation of Cultured Rat Astrocytes. Evidence for Reciprocal Upregulation of the mRNAs for GLP-2 and IGF-I Receptors

2009

View full text Add to dashboard Cite

show abstract

“…Previous studies in rats [48] and mice [76] showed that fasting for 1 or a couple of days resulted in atrophy of the small intestine but could be reversed by refeeding and that this refeeding adaptation was prevented upon antagonizing the GLP-2 receptor. Other studies found that intestinal atrophy seen in rodents and pigs after total parenteral nutrition [48,77] could be ameliorated by coinfusion of GLP-2 [41,77,78]. Because patients undergoing high-dose chemotherapy treatment often have low or no enteral nutrition for days during the first few weeks after transplantation, the direct toxic effects of chemotherapy could be aggravated through insufficient GLP-1 and GLP-2 secretion, leading to incomplete healing and regeneration of the intestinal epithelium.…”

Section: Discussionmentioning

confidence: 99%

Glucagon-Like Peptide-1 Is a Marker of Systemic Inflammation in Patients Treated with High-Dose Chemotherapy and Autologous Stem Cell Transplantation

Ebbesen

Kissow

Hartmann

et al. 2019

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

Autologous stem cell transplantation (ASCT) is challenged by side effects that may be propagated by chemotherapy-induced mucositis, resulting in bacterial translocation and systemic inflammation. Because gastrointestinal damage appears as an early event in this cascade of reactions, we hypothesized that markers reflecting damage to the intestinal barrier could serve as early predictive markers of toxicity. Glucagon-like peptide-1 (GLP-1), a wellknown regulator of blood glucose, has been found to promote intestinal growth and repair in animal studies. We investigated fasting GLP-1 plasma levels in 66 adults undergoing ASCT for lymphoma and multiple myeloma. GLP-1 increased significantly after chemotherapy, reaching peak levels at day +7 post-transplant (median, 8 pmol/L [interquartile range, 4 to 12] before conditioning versus 10 pmol/L [interquartile range, 6 to 17] at day +7; P = .007). The magnitude of the GLP-1 increase was related to the intensity of conditioning. GLP-1 at the day of transplantation (day 0) was positively associated with peak C-reactive protein (CRP) levels (46 mg/L per GLP-1 doubling, P < .001) and increase in days with fever (32% per GLP-1 doubling, P = .0058). Patients with GLP-1 above the median at day 0 had higher CRP levels from days +3 to +10 post-transplant than patients with lower GLP-1 (P .041) with peak values of 238 versus 129 mg/L, respectively. This study, which represents the first clinical investigation of fasting GLP-1 in relation to high-dose chemotherapy, provides evidence that GLP-1 plays a role in regulation of mucosal defenses. Fasting GLP-1 levels may serve as an early predictor of systemic inflammation and fever in patients receiving high-dose chemotherapy.

show abstract

“…Similar responses were reported in mice [ 9 ]. Likewise, it is well known that rodents and pigs receiving TPN experience severe intestinal atrophy [ 37 ; 38 ], which can be ameliorated by co-infusion with GLP-2 [ 38 ; 39 ]. However, patients with active inflammatory bowel disease were found to have higher levels of GLP-2 [ 40 ] and GLP-1 [ 41 ], and together with our earlier findings that both hormones were markedly increased in rats 2 days after 5-FU [ 17 ; 27 ], it seems that the hormones are also secreted in response to intestinal injury.…”

Section: Discussionmentioning

confidence: 99%

Endogenous glucagon-like peptide- 1 and 2 are essential for regeneration after acute intestinal injury in mice

et al. 2018

View full text Add to dashboard Cite

ObjectiveMucositis is a side effect of chemotherapy seen in the digestive tract, with symptoms including pain, diarrhoea, inflammation and ulcerations. Our aim was to investigate whether endogenous glucagon-like peptide -1 and -2 (GLP-1 and GLP-2) are implicated in intestinal healing after chemotherapy-induced mucositis.DesignWe used a transgenic mouse model Tg(GCG.DTR)(Tg) expressing the human diphtheria toxin receptor in the proglucagon-producing cells. Injections with diphtheria toxin ablated the GLP-1 and GLP-2 producing L-cells in Tg mice with no effect in wild-type (WT) mice. Mice were injected with 5-fluorouracil or saline and received vehicle, exendin-4, teduglutide (gly2-GLP-2), or exendin-4/teduglutide in combination. The endpoints were body weight change, small intestinal weight, morphology, histological scoring of mucositis and myeloperoxidase levels.ResultsAblation of L-cells led to impaired GLP-2 secretion; increased loss of body weight; lower small intestinal weight; lower crypt depth, villus height and mucosal area; and increased the mucositis severity score in mice given 5-fluorouracil. WT mice showed compensatory hyperproliferation as a sign of regeneration in the recovery phase. Co-treatment with exendin-4 and teduglutide rescued the body weight of the Tg mice and led to a hyperproliferation in the small intestine, whereas single treatment was less effective.ConclusionThe ablation of L-cells leads to severe mucositis and insufficient intestinal healing, shown by severe body weight loss and lack of compensatory hyperproliferation in the recovery phase. Co-treatment with exendin-4 and teduglutide could prevent this. Because both peptides were needed, we can conclude that both GLP-1 and GLP-2 are essential for intestinal healing in mice.

show abstract

The role of polyamines in glucagon-like peptide-2 prevention of TPN-induced gut hypoplasia

Cited by 6 publications

References 41 publications

Synergistic Effect of Glucagon-Like Peptide 2 (GLP-2) and of Key Growth Factors on the Proliferation of Cultured Rat Astrocytes. Evidence for Reciprocal Upregulation of the mRNAs for GLP-2 and IGF-I Receptors

Synergistic Effect of Glucagon-Like Peptide 2 (GLP-2) and of Key Growth Factors on the Proliferation of Cultured Rat Astrocytes. Evidence for Reciprocal Upregulation of the mRNAs for GLP-2 and IGF-I Receptors

Glucagon-Like Peptide-1 Is a Marker of Systemic Inflammation in Patients Treated with High-Dose Chemotherapy and Autologous Stem Cell Transplantation

Endogenous glucagon-like peptide- 1 and 2 are essential for regeneration after acute intestinal injury in mice

Contact Info

Product

Resources

About