Role of luminal nutrients and endogenous GLP-2 in intestinal adaptation to mid-small bowel resection

2003 ◽  
Vol 284 (4) ◽  
pp. G670-G682 ◽  
Author(s):  
Elizabeth M. Dahly ◽  
Melanie B. Gillingham ◽  
Ziwen Guo ◽  
Sangita G. Murali ◽  
David W. Nelson ◽  
...  
Keyword(s):  
Small Bowel ◽  
Adaptive Response ◽  
Bowel Resection ◽  
Intestinal Adaptation ◽  
Small Bowel Resection ◽  
Oral Feeding ◽  
Enterocyte Proliferation ◽  
Glucagon Like Peptide ◽  
Mucosal Growth

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.

scholarly journals Ret heterozygous mice have enhanced intestinal adaptation after massive small bowel resection

2012 ◽  
Vol 302 (10) ◽  
pp. G1143-G1150 ◽  
Author(s):  
Meredith C. Hitch ◽  
Jennifer A. Leinicke ◽  
Derek Wakeman ◽  
Jun Guo ◽  
Chris R. Erwin ◽  
...  
Keyword(s):  
Small Bowel ◽  
Bowel Resection ◽  
Intestinal Adaptation ◽  
Growth Factor Receptor ◽  
Small Bowel Resection ◽  
Compensatory Response ◽  
Protein Levels ◽  
Enterocyte Proliferation ◽  
Glucagon Like Peptide ◽  
Massive Small Bowel Resection

Intestinal adaptation is an important compensatory response to massive small bowel resection (SBR) and occurs because of a proliferative stimulus to crypt enterocytes by poorly understood mechanisms. Recent studies suggest the enteric nervous system (ENS) influences enterocyte proliferation. We, therefore, sought to determine whether ENS dysfunction alters resection-induced adaptation responses. Ret+/− mice with abnormal ENS function and wild-type (WT) littermates underwent sham surgery or 50% SBR. After 7 days, ileal morphology, enterocyte proliferation, apoptosis, and selected signaling proteins were characterized. Crypt depth and villus height were equivalent at baseline in WT and Ret+/− mice. In contrast after SBR, Ret+/− mice had longer villi (Ret+/− 426.7 ± 46.0 μm vs. WT 306.5 ± 7.7 μm, P < 0.001) and deeper crypts (Ret+/− 119 ± 3.4 μm vs. WT 82.4 ± 3.1 μm, P < 0.001) than WT. Crypt enterocyte proliferation was higher in Ret+/− (48.8 ± 1.3%) than WT (39.9 ± 2.1%; P < 0.001) after resection, but apoptosis rates were similar. Remnant bowel of Ret+/− mice also had higher levels of glucagon-like peptide 2 (6.2-fold, P = 0.005) and amphiregulin (4.6-fold, P < 0.001) mRNA after SBR, but serum glucagon-like peptide 2 protein levels were equal in WT and Ret+/− mice, and there was no evidence of increased c-Fos nuclear localization in submucosal neurons. Western blot confirmed higher crypt epidermal growth factor receptor (EGFR) protein levels (1.44-fold; P < 0.001) and more phosphorylated EGFR (2-fold; P = 0.003) in Ret+/− than WT mice after SBR. These data suggest that Ret heterozygosity enhances intestinal adaptation after massive SBR, likely via enhanced EGFR signaling. Reducing Ret activity or altering ENS function may provide a novel strategy to enhance adaptation attenuating morbidity in patients with short bowel syndrome.

Time-dependent intestinal adaptation and GLP-2 alterations after small bowel resection in rats

2001 ◽  
Vol 281 (3) ◽  
pp. G779-G785 ◽  
Author(s):  
K. Ljungmann ◽  
B. Hartmann ◽  
P. Kissmeyer-Nielsen ◽  
A. Flyvbjerg ◽  
J. J. Holst ◽  
...  
Keyword(s):  
Small Bowel ◽  
Growth Response ◽  
Bowel Resection ◽  
Intestinal Adaptation ◽  
Small Bowel Resection ◽  
Sham Operation ◽  
Morphological Adaptation ◽  
Entire Study ◽  
Glucagon Like Peptide

Existing data on morphological adaptation after small bowel resection are obtained by potentially biased methods. Using stereological techniques, we examined segments of bowel on days 0, 4, 7, 14, and 28 after 80% jejunoileal resection or sham operation in rats and correlated intestinal growth with plasma levels of glucagon-like peptide-2 (GLP-2). In the jejunum and ileum of the resected rats, the mucosal weight increased by 120 and 115% during the first week, and the weight of muscular layer increased by 134 and 83%, compared with sham-operated controls. The luminal surface area increased by 190% in the jejunum and by 155% in the ileum after 28 days. The GLP-2 level was increased by 130% during the entire study period in the resected rats. Small bowel resection caused a pronounced and persistent transmural growth response in the remaining small bowel, with the most prominent growth occurring in the jejunal part. The significantly elevated GLP-2 level is consistent with an important role of GLP-2 in the adaptive response.

The role of apoptosis during intestinal adaptation after small bowel resection

2000 ◽  
Vol 35 (1) ◽  
pp. 20-24 ◽  
Author(s):  
Carlo F.M. Welters ◽  
Femke E. Piersma ◽  
David M. Hockenbery ◽  
Erik Heineman Maastricht
Keyword(s):  
Small Bowel ◽  
Bowel Resection ◽  
Intestinal Adaptation ◽  
Small Bowel Resection

Enterocytic gene expression in intestinal adaptation: evidence for a specific cellular response

1996 ◽  
Vol 270 (1) ◽  
pp. G143-G152 ◽  
Author(s):  
D. C. Rubin ◽  
E. A. Swietlicki ◽  
J. L. Wang ◽  
B. D. Dodson ◽  
M. S. Levin
Keyword(s):  
Small Bowel ◽  
Adaptive Response ◽  
Cellular Response ◽  
Bowel Resection ◽  
Intestinal Adaptation ◽  
Small Bowel Resection ◽  
Mrna Levels ◽  
Fatty Acid Binding ◽  
Mrna And Protein Expression ◽  
Differentiation Status

After massive small bowel resection, the remnant gut epithelium undergoes an adaptive response marked by an increase in villus height, crypt depth, and crypt cell production rate. Although morphological features of gut adaptation have been well characterized, the differentiation status and response of epithelial cells populating the adaptive villus is unclear. To address these issues, cell-specific and spatial patterns of expression of a set of enterocytic genes were characterized in rats after 70% small bowel resection. The liver and intestinal (I) fatty acid binding protein (FABP) and apolipoprotein A-I (apo A-I) and apo A-IV genes were studied because they exhibit unique regional and cell-specific patterns of expression in the developing and adult gut. At 48 h after surgery, apo A-IV and I-FABP mRNA levels were increased up to 3.5-fold in adaptive remnant ileum compared with sham-operated or sham-resected control ileum. In situ hybridization and immunohistochemical analyses revealed a marked increase in enterocytic apo A-IV mRNA and protein expression in the adaptive ileum, from villus base to tip but not in crypts. By 1 wk after resection, apo A-IV, but not I-FABP, mRNA levels remained elevated in remnant ileum, although duodenal I-FABP mRNA levels were still increased. In contrast, apo A-I mRNA levels were not significantly induced. These results indicate that the enterocyte can respond acutely to loss of small bowel surface area by increasing expression of several genes. This compensatory enterocytic response is spatially (from duodenum to ileum) and temporally regulated. These results suggest initiation of the adaptive response occurs by way of a complex set of molecular pathways involving villus and crypt cells.

759 Low-Dose Glucagon-Like Peptide-2 Augments Intestinal Adaptation and Proglucagon Expression in a Rat Model of MID-Small Bowel Resection

2008 ◽  
Vol 134 (4) ◽  
pp. A-111
Author(s):  
Matthew C. Koopmann ◽  
David W. Nelson ◽  
Sangita G. Murali ◽  
Xiaowen Liu ◽  
Mark S. Brownfield ◽  
...  
Keyword(s):  
Small Bowel ◽  
Rat Model ◽  
Low Dose ◽  
Bowel Resection ◽  
Intestinal Adaptation ◽  
Small Bowel Resection ◽  
Glucagon Like Peptide

Intestinal adaptation and enterocyte apoptosis following small bowel resection is p53 independent

1999 ◽  
Vol 277 (3) ◽  
pp. G717-G724 ◽  
Author(s):  
Cathy E. Shin ◽  
Richard A. Falcone ◽  
Christopher J. Kemp ◽  
Christopher R. Erwin ◽  
David A. Litvak ◽  
...  
Keyword(s):  
Small Bowel ◽  
Protein Content ◽  
Bowel Resection ◽  
Intestinal Adaptation ◽  
Small Bowel Resection ◽  
Apoptotic Bodies ◽  
Wild Type ◽  
Villus Height ◽  
Enterocyte Proliferation ◽  
Enterocyte Apoptosis

Adaptation following small bowel resection (SBR) signals enterocyte proliferation and apoptosis. Because p53-induced p21waf1/cip1may be important for apoptosis in many cells, we hypothesized that these genes are required for increased enterocyte apoptosis during adaptation. Male C57BL/6 (wild-type) or p53-null mice underwent 50% proximal SBR or sham operation (bowel transection-reanastomosis). Adaptation (DNA-protein content, villus height-crypt depth, enterocyte proliferation), appearance of apoptotic bodies, and p53 and p21waf1/cip1protein expression were measured in the ileum after 5 days. Adaptation was equivalent after SBR in both wild-type and p53-null mice as monitored by significantly increased ileal DNA-protein content, villus height, and enterocyte proliferation. The number of crypt apoptotic bodies increased significantly after SBR evenly in both wild-type and p53-null mice. In the p53-null mice, SBR substantially induced the expression of p21waf1/cip1protein in villus enterocytes. The p53-independent induction of p21waf1/cip1may account for the similar intestinal response to SBR between wild-type and p53-null mice. Intestinal adaptation and increased enterocyte apoptosis following intestinal resection occur via a p53-independent mechanism.

Gut adaptation and the insulin-like growth factor system: regulation by glutamine and IGF-I administration

1996 ◽  
Vol 271 (5) ◽  
pp. G866-G875 ◽  
Author(s):  
T. R. Ziegler ◽  
M. P. Mantell ◽  
J. C. Chow ◽  
J. L. Rombeau ◽  
R. J. Smith
Keyword(s):  
Growth Factor ◽  
Small Bowel ◽  
Dna Content ◽  
Bowel Resection ◽  
Synergistic Effects ◽  
Intestinal Adaptation ◽  
Intestinal Resection ◽  
Small Bowel Resection ◽  
Insulin Like Growth Factor ◽  
Igf I

Intestinal adaptation after extensive small bowel resection in rats is augmented by the provision of diets supplemented with the amino acid glutamine (Gln) or by administration of insulin-like growth factor-I (IGF-I). The goal of this study was to investigate potential synergistic effects of Gln and IGF-I on postresection ileal hyperplasia. Rats underwent 80% small bowel resection (SBR) and then were fed low-Gln or L-Gln-enriched diets and subcutaneously given recombinant human IGF-I or vehicle for 7 days. Gln and IGF-I each significantly enhanced adaptive ileal hyperplasia (DNA content) compared with rats receiving vehicle and low-Gln diet. Ileal DNA content was highest when IGF-I was administered together with Gln supplementation. Combined IGF-I plus Gln synergistically increased ileal weight and protein content. This was associated with higher plasma concentrations of IGF-I and Gln than observed when IGF-I or Gln was given individually. Ileal IGF-I mRNA expression rose nearly twofold during gut adaptation after SBR; this response was augmented with IGF-I administration but was unaltered by Gln feeding. In contrast, dietary Gln, but not IGF-I therapy, prevented a decrease in hepatic IGF-I mRNA induced by SBR. We conclude that parenteral IGF-I and enteral Gln have both individual and synergistic effects on ileal adaptation after massive small intestinal resection. These findings support the concept that specific gut-trophic nutrients and growth factors may be combined to enhance intestinal adaptation and possibly reduce the severity of short bowel syndrome after intestinal resection.

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