GLP-2 Levels in Infants With Intestinal Dysfunction

Sigalet, David L.; Martin, Gary R.; Meddings, Jon; Hartman, Bolette; Holst, Jens J.

doi:10.1203/01.pdr.0000134250.80492.ec

Cited by 69 publications

(66 citation statements)

References 30 publications

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“…role in raising plasma GLP-2 levels post-intestinal resection in neonates (23,24). The developing colon may be unable to sustain progressive or adequate compensatory increase in plasma GLP-2 levels postresection, as compared with remnant ileum.…”

Section: Discussionmentioning

confidence: 99%

“…Correlations between plasma GLP-2 levels and the total amount of lipid infused or the amount absorbed were also identified. In studying GLP-2 levels in human infants with intestinal resection, it was not possible to control for the amount of nutrition being delivered, and a correlation between GLP-2 levels and enteral tolerance and fat absorption was also shown (23). This is a complex issue because the role of GLP-2 in adaptation logically means enteral tolerance may be better in those piglets and infants that have higher circulating levels.…”

Section: Glp-2 In Neonatal Short Bowel Syndromementioning

confidence: 99%

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Role of glucagon-like peptide–2 deficiency in neonatal short-bowel syndrome using neonatal piglets

et al. 2013

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Background: Short-bowel syndrome (SBS) is the most common cause of neonatal intestinal failure. Recovery requires intestinal adaptation, dependent on enteral nutrition (EN) and growth factors such as glucagon-like peptide-2 (GLP-2), which is secreted from L cells in the ileum. Neonatal SBS often results in loss of ileum; therefore, we hypothesized that without ileum, endogenous GLP-2 production would be inadequate to promote adaptation. We compared endogenous GLP-2 production and adaptation in neonatal animals with SBS, with and without ileum. Methods: Neonatal piglets (4-6 d) were randomized to 75% mid-intestinal resection, 75% distal-intestinal resection, or sham control without resection. Postoperatively, all piglets commenced parenteral nutrition (PN), tapering as EN was increased to maintain specific growth. results: The resected SBS piglets developed intestinal failure, requiring a longer duration of PN support and experiencing fat malabsorption. The piglets without ileum were not able to wean from PN during the study and did not show adaptation, specifically growth in intestinal length or crypt hyperplasia on histology of the jejunum. Adaptation was observed in the resected SBS piglets with ileum, and these piglets also had an increased plasma GLP-2 level that was not observed in piglets without ileum. conclusion: SBS piglets with ileum undergo adaptation associated with increased endogenous GLP-2 production. SBS piglets without ileum undergo limited adaptation and severe intestinal failure, requiring prolonged PN support. This appears to be related to a deficiency in endogenous GLP-2 production. n eonatal intestinal failure secondary to short-bowel syndrome (SBS) has a particularly poor outcome. It is most common in preterm infants, and necrotizing enterocolitis is the most common cause (1-3). Necrotizing enterocolitis usually results in loss of ileum and right colon and carries a significant mortality (4).After intestinal resection, adaptation of the remnant intestine is essential for survival, compensating for the reduced absorptive surface area, both structurally and functionally (5). This process is regulated by several factors, including the stage of intestinal development, site and length of resection, the underlying disease, nutritional status, and gut-derived hormones and growth factors (6). Among the growth factors, glucagon-like peptide-2 (GLP-2) is considered to have an important role in inducing small-intestinal adaptation after resection. GLP-2 acts specifically at the GLP-2 receptor (GLP-2R), which is expressed throughout the small and large intestines but with greatest concentration in the jejunum (7). GLP-2 is uniquely trophic for the intestine (8). It can stimulate residual small-intestinal adaptation by increasing crypt cell proliferation and inhibiting apoptosis, thereby increasing villus height, crypt depth, mucosal mass, and overall small-intestinal length and weight (9-11). Functionally, GLP-2 increases activities of mucosal enzymes and therefore increases digestion and absorption (...

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Section: Discussionmentioning

confidence: 99%

Section: Glp-2 In Neonatal Short Bowel Syndromementioning

confidence: 99%

Role of glucagon-like peptide–2 deficiency in neonatal short-bowel syndrome using neonatal piglets

et al. 2013

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“…On the other hand, plasma GLP-2 levels appear to vary with intestinal mucosal condition and injury. However, although changes in various conditions of the intestinal mucosa are now being widely studied, [21][22][23] the relationship between plasma GLP-2 levels and intestinal mucosal injury induced by various drugs, including antineoplastic agents, has yet to be clearly determined. Moreover, no standard methods of diagnosis or therapeutic protocols exist for chemotherapy-induced enteritis, and further research into new therapeutic avenues for treatment or prevention of this intestinal injury is needed.…”

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confidence: 99%

Correlation between Plasma Glucagon-Like Peptide 2 Levels and Proliferative Makers in Small Intestinal Injury in Rats Induced by Methotrexate Administration

Hirotani

Yamamoto

Ikeda

et al. 2006

Biological & Pharmaceutical Bulletin

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Chemotherapy is an important primary and adjuvant therapy for cancer patients. The cytotoxicity of antineoplastic agents affects not only tumor cells but also rapidly proliferating normal cells, such as those of the gastrointestinal mucosa.1) Common complications of chemotherapy thus include stomatitis and enterocolitis.2) Methotrexate (MTX) is an antimetabolite drug that blocks the production of biologically active forms of folic acid. The major lesions resulting from its cytotoxic effects occur in bone marrow and the intestinal tract. High doses of MTX cause severe enterocolitis, weight loss, anorexia and intestinal atrophy. 3,4) The mucosa of the digestive tract, particularly that of the small intestine, is a critical site of action of anticancer agents including MTX, as the undifferentiated epithelial cells in the crypts, which ensure continuous and relatively fast regeneration of the epithelium, are particularly sensitive to these cytostatic drugs.5-7) Patients receiving these anticancer agents frequently experience gastrointestinal side effects, such as nausea, vomiting and diarrhea, reflecting gastrointestinal mucosal damage or enterocolitis.2) Chemotherapy-associated diarrhea may be problematic, and even life threatening, if complicated by mucosal ulceration and inflammatory changes. Moreover, patients with advanced malignancy often suffer from malnutrition, which increases toxicity and decreases tumor responses to treatment,2) and such conditions can be dose limiting in therapeutic regimens. A method for prediction of adverse reactions to chemotherapy is thus needed to avoid their occurrence.Gastrointestinal mucosal integrity is regulated by several growth factors and cytokines, such as transforming growth factors-beta and IL-11.8-11) Glucagon-like peptide 2 (GLP-2) has been demonstrated to have intestinotrophic effects. 12)GLP-2, a 33-amino acid peptide member of a family of proglucagon-derived peptides (PGDP) that also includes enteroglucagon, is secreted from L-type entero-endocrine cells of the distal small intestine and colon.12) GLP-2 increases crypt cell proliferation and decreases the rate of apoptosis in small intestinal epithelium.13) Acute or chronic administration of GLP-2 induces functional changes in the intestine, improving its capacity for nutrient absorption. [13][14][15] In addition, GLP-2 treatment has been shown to enhance intestinal adaptation following major small bowel resection, 16,17) to prevent 18) and to reduce the severity of dextran sulfate-induced colitis 19) and indomethacin-induced enteritis 20) in animal models. On the other hand, plasma GLP-2 levels appear to vary with intestinal mucosal condition and injury. However, although changes in various conditions of the intestinal mucosa are now being widely studied, [21][22][23] the relationship between plasma GLP-2 levels and intestinal mucosal injury induced by various drugs, including antineoplastic agents, has yet to be clearly determined. Moreover, no standard methods of diagnosis or therapeutic protocols exist for chemo...

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“…Few human studies have been performed [10][11][13][14][15][16] , but the results indicate that GLP-2 administration may represent a new therapeutic approach for patients with gastrointestinal problems. Sigalet et al [16] studied human infants with intestinal dysfunction after surgical resection.…”

Section: Discussionmentioning

confidence: 99%

“…Sigalet et al [16] studied human infants with intestinal dysfunction after surgical resection. They demonstrated a possible correlation between postprandial GLP-levels and residual small bowel length and nutrient absorption.…”

Section: Discussionmentioning

confidence: 99%

Glucagon-Like Peptide-2 in Umbilical Cord Blood from Mature Infants

et al. 2006

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Background: Glucagon-like peptide-2 (GLP-2) seems to be a highly specific intestinotrophic mediator. From animal studies, GLP-2 is known to increase in the early neonatal period before it falls to adult level. No studies in newborn infants addressing this specific subject have been published so far. Objectives: To measure GLP-2 concentrations in umbilical cord blood from healthy mature infants and to assess any influence from the processes associated with spontaneous birth to GLP-2 production. Subjects: Twenty-one children delivered by elective cesarean section for maternal reasons and 18 children delivered spontaneously vaginally and without complications were included. Gestational age (GA) was median (range) 38.7 (40.7–37.1) weeks and 40.2 (41.9–38) weeks, and birth weight was median (range) 3,210 (4,820–2,100) g and 3,396 (4,225–3,050) g, respectively. The infants had no diagnosed diseases or malformations. Methods: Umbilical cord blood was collected shortly after birth. Plasma was separated and GLP-2 immunoreactivity was measured with a specific NH₂-terminal radioimmunoassay. Results: GLP-2 was detected in all samples. Mean values ±SD were 16.7 ± 3.9 pmol/l and range was 32–11 pmol/l, which is comparable to adult fasting levels. No significant correlation to birth weight (p = 0.087) or to cesarean section (p = 0.059) was found. In multiple linear regression analysis (GLP-2 vs. GA + cesarean section), neither vaginal delivery nor GA were statistically significantly related to the level of GLP-2 (p = 0.28 and 0.18), respectively. Conclusions: GLP-2 is present in human cord blood by the time of birth. The level of GLP-2 is comparable to adult fasting levels. Spontaneous birth at most induces a minor increase in GLP-2 in term infants. In the narrow age interval studied, no significant effect of maturation was seen.

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GLP-2 Levels in Infants With Intestinal Dysfunction

Cited by 69 publications

References 30 publications

Role of glucagon-like peptide–2 deficiency in neonatal short-bowel syndrome using neonatal piglets

Role of glucagon-like peptide–2 deficiency in neonatal short-bowel syndrome using neonatal piglets

Correlation between Plasma Glucagon-Like Peptide 2 Levels and Proliferative Makers in Small Intestinal Injury in Rats Induced by Methotrexate Administration

Glucagon-Like Peptide-2 in Umbilical Cord Blood from Mature Infants

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