Glucagon-Like Peptide 2 Stimulates Postresection Intestinal Adaptation in Preterm Pigs by Affecting Proteins Related to Protein, Carbohydrate, and Sulphur Metabolism

To elucidate the role of luminal nutrients and glucagon-like peptide-2 (GLP-2) in intestinal adaptation, rats were subjected to 70% midjejunoileal resection or ileal transection and were maintained with total parenteral nutrition (TPN) or oral feeding. TPN rats showed small bowel mucosal hyperplasia at 8 h through 7 days after resection, demonstrating that exogenous luminal nutrients are not essential for resection-induced adaptation when residual ileum and colon are present. Increased enterocyte proliferation was a stronger determinant of resection-induced mucosal growth in orally fed animals, whereas decreased apoptosis showed a greater effect in TPN animals. Resection induced significant transient increases in plasma bioactive GLP-2 during TPN, whereas resection induced sustained increases in plasma GLP-2 during oral feeding. Resection-induced adaptive growth in TPN and orally fed rats was associated with a significant positive correlation between increases in plasma bioactive GLP-2 and proglucagon mRNA expression in the colon of TPN rats and ileum of orally fed rats. These data support a significant role for endogenous GLP-2 in the adaptive response to mid-small bowel resection in both TPN and orally fed rats.

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Glucagon‐like Peptide‐2 Therapy Improves Outcomes of Intestinal Adaptation and Decreases Relative Apoptosis in a Distal Intestinal Resection Neonatal Piglet Model of Short Bowel Syndrome

The FASEB Journal ◽

10.1096/fasebj.27.1_supplement.867.4 ◽

2013 ◽

Vol 27 (S1) ◽

Author(s):

Megha Suri ◽

Justine M. Turner ◽

Patrick N. Nation ◽

Pamela Wizzard ◽

Patricia L. Brubaker ◽

...

Keyword(s):

Short Bowel Syndrome ◽

Intestinal Adaptation ◽

Intestinal Resection ◽

Short Bowel ◽

Neonatal Piglet ◽

Glucagon Like Peptide

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Glucagon-like peptide-2 and mouse intestinal adaptation to a high-fat diet

Journal of Endocrinology ◽

10.1530/joe-12-0500 ◽

2013 ◽

Vol 217 (1) ◽

pp. 11-20 ◽

Cited By ~ 40

Author(s):

Sara Baldassano ◽

Antonella Amato ◽

Francesco Cappello ◽

Francesca Rappa ◽

Flavia Mulè

Keyword(s):

High Fat Diet ◽

Caspase 3 ◽

Potential Role ◽

Intestinal Adaptation ◽

Cell Number ◽

Standard Diet ◽

High Fat ◽

Villus Height ◽

Glucagon Like Peptide

Endogenous glucagon-like peptide-2 (GLP2) is a key mediator of refeeding-induced and resection-induced intestinal adaptive growth. This study investigated the potential role of GLP2 in mediating the mucosal responses to a chronic high-fat diet (HFD). In this view, the murine small intestine adaptive response to a HFD was analyzed and a possible involvement of endogenous GLP2 was verified using GLP2 (3–33) as GLP2 receptor (GLP2R) antagonist. In comparison with animals fed a standard diet, mice fed a HFD for 14 weeks exhibited an increase in crypt–villus mean height (duodenum, 27.5±3.0%; jejunum, 36.5±2.9%;P<0.01), in the cell number per villus (duodenum, 28.4±2.2%; jejunum, 32.0±2.9%;P<0.01), and in Ki67-positive cell number per crypt. No change in the percent of caspase-3-positive cell in the villus–crypt was observed. The chronic exposure to a HFD also caused a significant increase in GLP2 plasma levels and in GLP2R intestinal expression. Daily administration of GLP2 (3–33) (30–60 ng) for 4 weeks did not modify the crypt–villus height in control mice. In HFD-fed mice, chronic treatment with GLP2 (3–33) reduced the increase in crypt–villus height and in the cell number per villus through reduction of cell proliferation and increase in apoptosis. This study provides the first experimental evidence for a role of endogenous GLP2 in the intestinal adaptation to HFD in obese mice and for a dysregulation of the GLP2/GLP2R system after a prolonged HFD.

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Synergy of glucagon-like peptide-2 and epidermal growth factor coadministration on intestinal adaptation in neonatal piglets with short bowel syndrome

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00281.2016 ◽

2017 ◽

Vol 312 (4) ◽

pp. G390-G404 ◽

Cited By ~ 11

Author(s):

David W. Lim ◽

Crystal L. Levesque ◽

Donna F. Vine ◽

Mitsuru Muto ◽

Jacob R. Koepke ◽

...

Keyword(s):

Growth Factors ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Short Bowel Syndrome ◽

Intestinal Adaptation ◽

Villus Height ◽

Short Bowel ◽

Intestinal Length ◽

Epidermal Growth ◽

Glucagon Like Peptide

Glucagon-like peptide-2 (GLP-2) and epidermal growth factor (EGF) treatment enhance intestinal adaptation. To determine whether these growth factors exert synergistic effects on intestinal growth and function, GLP-2 and EGF-containing media (EGF-cm) were administered, alone and in combination, in neonatal piglet models of short bowel syndrome (SBS). Neonatal Landrace-Large White piglets were block randomized to 75% midintestinal [jejunoileal (JI) group] or distal intestinal [jejunocolic (JC) group] resection or sham control, with 7-day infusion of saline (control), intravenous human GLP-2 (11 nmol·kg−1·day−1) alone, enteral EGF-cm (80 μg·kg−1·day−1) alone, or GLP-2 and EGF-cm in combination. Adaptation was assessed by intestinal length, histopathology, Üssing chamber analysis, and real-time quantitative PCR of intestinal growth factors. Combined EGF-cm and GLP-2 treatment increased intestinal length in all three surgical models ( P < 0.01). EGF-cm alone selectively increased bowel weight per length and jejunal villus height in the JI group only. The JC group demonstrated increased intestinal weight and villus height ( P < 0.01) when given either GLP-2 alone or in combination with EGF-cm, with no effect of EGF-cm alone. Jejunal permeability of mannitol and polyethylene glycol decreased with combination therapy in both SBS groups ( P < 0.05). No difference was observed in fat absorption or body weight gain. IGF-1 mRNA was differentially expressed in JI vs. JC piglets with treatment. Combined treatment with GLP-2 and EGF-cm induced intestinal lengthening and decreased permeability, in addition to the trophic effects of GLP-2 alone. Our findings demonstrate the benefits of novel combination GLP-2 and EGF treatment for neonatal SBS, especially in the JC model representing most human infants with SBS. NEW & NOTEWORTHY Glucagon-like peptide-2 (GLP-2) and epidermal growth factor (EGF) are intestinotrophic, with demonstrated benefit in both animal models and human studies of short bowel syndrome (SBS). The current research shows that over and above known trophic effects, the combination of GLP-2 and EGF synergistically lengthens the bowel in neonatal piglet models of SBS. Most notable benefit occurred with resection of the terminal ileum, the common clinical anatomy seen in neonatal SBS and associated with least de novo lengthening postsurgery.

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