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Published in:

01-09-2011 | Original Article

Peptide Absorption After Massive Proximal Small Bowel Resection: Mechanisms of Ileal Adaptation

Authors: Hisham G. Qandeel, Fernando Alonso, David J. Hernandez, Srivats Madhavan, Judith A. Duenes, Ye Zheng, Michael G. Sarr

Published in: Journal of Gastrointestinal Surgery | Issue 9/2011

Abstract

Background

Protein absorption occurs as di- and tri-peptides via H⁺/peptide co-transporter-1 (PepT1).

Aim

The aim of this study is to identify mechanisms of ileal adaptation after massive proximal enterectomy.

Hypothesis

Ileal adaptation in uptake of peptides is mediated through upregulation of PepT1 gene expression.

Study Design

Rats underwent 70% jejunoileal resection. Total mucosal cellular levels of messenger RNA (mRNA) and protein and transporter-mediated uptake per centimeter of the di-peptide glycyl-sarcosine (Gly-Sar) were compared in remnant ileum 1 and 4 weeks postoperatively to control and to 1-week sham laparotomy rats. Histomorphology, food consumption, and weights of rats were monitored.

Results

After 70% resection, although mRNA per cell for PepT1 decreased at 1 week (p = 0.002), expression of mRNA at 4 weeks and protein at 1 and 4 weeks in remnant ileum were unchanged (p > 0.1). Ileal Gly-Sar uptake (V _max—nanomoles per centimeter per minute, i.e., number of transporters per centimeter) increased at 1 and 4 weeks compared to control and 1-week sham (p < 0.05 each); K _m (i.e., transporter function) was unchanged. Villous heights (millimeters) in remnant ileum increased at 1- and 4-week time points over controls (0.45 and 0.57 vs 0.21, resp; p < 0.001).

Conclusions

Ileal adaptation to proximal resection for peptide absorption occurs through cellular proliferation (hyperplasia) and not through cellular upregulation of PepT1 mRNA or protein per enterocyte.

Wilmore DW, Robinson MK. Short bowel syndrome. World J Surg 2000; 24:1486–92PubMedCrossRef

Vanderhoof JA, Langnas AN. Short-bowel syndrome in children and adults. Gastroenterology 1997;113:1767–78.PubMedCrossRef

Jackson C, Buchman AL. Advances in the management of short bowel syndrome. Curr Gastroenterol Rep. 2005;7(5):373–8.PubMedCrossRef

Keller J, Panter H, Layer P. Management of the short bowel syndrome after extensive small bowel resection. Best Pract Res Clin Gastroenterol. 2004;18(5):977–92.PubMed

Sundaram A, Koutkia P, Apovian, C. Nutritional management of short bowel syndrome in adults. J Clin Gastroenterol. 2002; 34 (3):207–220PubMedCrossRef

Scolapio JS, Camilleri M, Fleming CR. Gastrointestinal motility considerations in patients with short-bowel syndrome. Dig Dis 1997; 15:253–62.PubMedCrossRef

Drozdowski LA, Clandinin MT, Thomson AB. Morphological, kinetic, membrane biochemical and genetic aspects of intestinal enteroplasticity. World J Gastroenterol 2009; 15(7):774–87PubMedCrossRef

Haxhija EQ, Yang H, Spencer AU, Sun X, Teitelbaum DH. Intestinal epithelial cell proliferation is dependent on the site of massive small bowel resection. Pediatr Surg Int 2007; 23:379–90.PubMedCrossRef

Baksheev L, Fuller PJ. Gene expression in the adapting small bowel after massive small bowel resection. J Gastroenterol 2006; 41:1041–1052.PubMedCrossRef

10.

Weale AR, Edwards AG, Bailey M, Lear PA. Intestinal adaptation after massive intestinal resection. Postgrad Med J 2005;81(953):178–84.PubMedCrossRef

11.

Martin GR, Wallce LE, Sigalet DL. Glucagon-like peptide-2 induces intestinal adaptation in parenterally fed rats with short bowel syndrome. Am J Physiol Gastrointest Liver Physiol 2004; 286:G964–G972.PubMedCrossRef

12.

Albert V, Young GP. Differentiation status of rat enterocytes after intestinal adaptation to jejunoileal bypass. Gut 1992; 33(12):1638–1643.PubMedCrossRef

13.

Iqbal CW, Qandeel HG, Zheng Y, Duenes JA, Sarr MG. Mechanisms of ileal adaptation for glucose absorption after proximal-based small bowel resection. J Gastrointest Surg 2008;12:1854–64PubMedCrossRef

14.

Madhavan S, Scow JS, Nagao M, Zhen Y, Duenes JA, Sarr MG. Intestinal adaptation for oligopeptide absorption via PepT1 after massive (70%) mid small bowel resection. J Gastrointest Surg 15:240–249, 2011.PubMedCrossRef

15.

Adibi SA. The oligopeptide transporter (PEPT1) in human intestine: biology and function. Gastroenterology 1997;113:332–340.PubMedCrossRef

16.

Saito H, Okuda M, Terada T, Sasaki S, Inui K. Cloning and characterization of a rat H⁺/peptide cotransporter mediating absorption of β-lactam antibiotics in the intestine and kidney. J Pharmacol Exp Ther 1995;275:1631–1637.PubMed

17.

Daniel H. Molecular and integrative physiology of intestinal peptide transport. Ann Rev Physiol 2004;66:361–384.CrossRef

18.

Adibi SA. Regulation of expression of the intestinal oligopeptide transporter (Pept-1) in health and disease. Am J Physiol 2003;285:G779–G788.

19.

Pan X, Terada T, Irie M, Saito H, Inui K. Diurnal rhythm of H⁺-peptide cotransporter in rat small intestine. Am J Physiol 2002;283:G57–G64.

20.

Qandeel HG, Duenes JA, Zheng Y, Sarr MG. Diurnal expression and function of peptide transporter 1 (PEPT1). J Surg Res 2009;156(1):123–8PubMedCrossRef

21.

Qandeel HQ, Alonso F, Hernandez DJ, Duenes JA, Zheng Y, Scow JS, Sarr MG. Role of vagal innervation in diurnal rhythm of intestinal peptide transporter 1 (PEPT1). J Gastrointest Surg (2009) 13:1976–1985PubMedCrossRef

22.

Matthews DM, Grandy RH, Taylor E, Burston D. Influx of two dipeptides, glycylsarcosine and L-glutamyl-L-glutamic acid, into hamster jejunum in vitro. Clin Sci 1979;56:15.PubMed

23.

Nielsen CU, Amstrup J, Steffansen B, Frokjaer S, and Brodin B. Epidermal growth factor inhibits glycylsarcosine transport and hPepT1 expression in a human intestinal cell line. Am J Physiol Gastrointest Liver Physiol 281: G191–G199, 2001.PubMed

24.

Ashida K, Katsura T, Motohashi H, Saito H, and Inui K. Thyroid hormone regulates the activity and expression of the peptide transporter PEPT1 in Caco-2 cells. Am J Physiol Gastrointest Liver Physiol 282: G617–G623, 2002.PubMed

25.

Avissar NE, Ziegler TR, Wang HT, Gu LH, Miller JH, Iannoli P, Leibach FH, Ganapathy V, Sax HC. Growth factors regulation of rabbit sodium-dependent neutral amino acid transporter ATB0 and oligopeptide transporter 1 mRNAs expression after enterectomy. J Parenter Enteral Nutr 2001;25:65–72.CrossRef

26.

Ogihara H, Suzuki T, Inui K, Takata K. Peptide transporter in the rat small intestine: ultrastructural localization and the effect of starvation and administration of amino acids. Histochem J 1999;31:169–174.PubMedCrossRef

27.

Affleck JA, Helliwell PA, Kellett GL. Immunocytochemical detection of GLUT2 at the rat intestinal brush-border membrane. J Histochem Cytochem 2003; 51(11):1567–74.PubMedCrossRef

28.

Au A, Gupta A, Cheeseman CI. Rapid insertion of GLUT2 into the rat jejunal brush-border membrane promoted by glucagon-like peptide. Biochem J 2002; 367:247–254.PubMedCrossRef

29.

Helliwell PA, Richardson M, Kellett GL, et al. Stimulation of fructose transport across intestinal brush-border membrane by PMA is mediated by GLUT2 and dynamically regulated by protein kinase C. Biochem J 2000; 350:149–154.PubMedCrossRef

30.

Zheng Y, Duenes JA, Qandeel HG, Sarr MG. Translocation of Transfected GLUT2 to the Apical Membrane in Rat Intestinal IEC-6 Cells. Gastroenterology (Abstract) 2009; 136 (1), A95

31.

Zheng Y, Duenes JA, Qandeel HG, Sarr MG. Glucose-dependent translocation of GLUT2 in human intestinal CACO-2 cells. Gastroenterology (Abstract) 2009; 136 (1), A877.

32.

Scow JS, Tavakkolizadeh A, Zheng Y, Sarr MG. Acute “adaptation” by the small intestinal enterocyte: a post-transcriptional mechanism involving apical translocation of nutrient transporters. Surgery 2011; 149(5):601–5.PubMedCrossRef

Title: Peptide Absorption After Massive Proximal Small Bowel Resection: Mechanisms of Ileal Adaptation
Authors: Hisham G. Qandeel
Fernando Alonso
David J. Hernandez
Srivats Madhavan
Judith A. Duenes
Ye Zheng
Michael G. Sarr
Publication date: 01-09-2011
Publisher: Springer-Verlag
Published in: Journal of Gastrointestinal Surgery / Issue 9/2011
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI: https://doi.org/10.1007/s11605-011-1581-z

At a glance: The ONWARDS insulin icodec trials

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Peptide Absorption After Massive Proximal Small Bowel Resection: Mechanisms of Ileal Adaptation

Abstract

Background

Aim

Hypothesis

Study Design

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Aim

Hypothesis

Study Design

Results

Conclusions

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