Abstract
Background: Epidermal growth factor (EGF) signals enterocyte proliferation via extracellular
regulated kinases (ERKs). Because glutamine is required for EGF-stimulated proliferation
and stimulates ERKs in intestinal cell culture, we hypothesized that glutamine and
the EGF-related peptide transforming growth factor–alpha (TGF-α) would synergistically
enhance repair associated with stimulation of ERKs. Methods: Thiry-Vella loops were created in juvenile pigs. One half of the loop was subjected
to 2 hours of ischemia, and the other half served as control. Loops were infused daily
with Ringer's solution containing 140 mmol/L glucose, 140 mmol/L glutamine, 140 mmol/L
glucose plus 60 μg/L TGF-α, or 140 mmol/L glutamine plus 60 μg/L TGF-α. Results: After 2 hours of ischemia, complete villous epithelial sloughing was present. By
18 hours, villous epithelium had fully restituted, but villi remained stunted until
144 hours after injury. Glutamine + TGF-α triggered sustained increases in ERK activity
compared with glucose-treated tissues (maximal at 18 hours), whereas glutamine alone
or glucose + TGF-α caused only transient elevations in ERK activity. By 72 hours,
villous surface area had increased to normal values with glutamine plus TGF-α treatment,
whereas villi remained stunted with glucose alone, glutamine alone, or glucose plus
TGF-α. Conclusions: Glutamine plus TGF-α treatment restored mucosal architecture within 72 hours of severe
ischemic injury associated with sustained elevations in ERK activity. (Surgery 1999;125:186-94.)
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to SurgeryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Is reperfusion injury an important cause of mucosal damage following porcine intestinal ischemia?.Surgery. 1997; 121: 526-534
- Effect of glutamine-supplemented total parenteral nutrition on recovery of the small intestine after starvation atrophy.JPEN. 1993; 17: 165-170
- Gut glutamine metabolism.JPEN. 1990; 14: 45S-50S
- The influence of parenteral glutamine and branched-chain amino acids on total parenteral nutrition-induced atrophy of the gut.JPEN. 1993; 17: 348-354
- Glutamine dipeptide-supplemented parenteral nutrition maintains intestinal function in the critically ill.Gastro-enterology. 1994; 107: 1595-1601
- Glutamine enhancement of structure and function in transplanted small intestine in the rat.JPEN. 1993; 17: 47-55
- Effect of a glutamine-supplemented enteral diet on methotrexate-induced enterocolitis.JPEN. 1988; 12: 325-331
- Oral glutamine accelerates healing of the small intestine and improves outcome after whole abdominal radiation.Arch Surg. 1990; 125: 1040-1045
- Prophylactic glutamine protects the intestinal mucosa from radiation injury.Cancer. 1990; 66: 62-68
- Insulin-like growth factor-I (IGF-I) and glutamine improve structure and function in the small bowel allograft.J Surg Res. 1995; 59: 6-12
- Glutamine is essential for epidermal growth factor–stimulated intestinal cell proliferation.Surgery. 1993; 114: 147-154
- L-Glutamine stimulates intestinal cell proliferation and activates mitogen-activated protein kinases.Am J Physiol. 1997; 272: 943-953
- Insulin-like growth factor-I and epidermal growth factor interact to regulate growth and gene expression in IEC-6 intestinal epithelial cells.Mol Endocrinol. 1995; 9: 1157-1165
- Signal transduction from cell surface to nucleus in development of disease.FASEB J. 1992; 6: 2581-2590
- Epidermal growth factor-related peptides and their relevance to gastrointestinal pathophysiology.Gastroenterology. 1995; 108: 564-580
- Villous atrophy, crypt hyperplasia, cellular infiltration, and impaired glucose-NA absorption in enteric cryptosporidiosis of pigs.Gastroenterology. 1990; 98: 1129-1140
- Migration of IEC-6 cells: a model for mucosal healing.Am J Physiol. 1992; 263: G426-G435
- Villus contraction aids repair of intestinal epithelium after injury.Am J Physiol. 1989; 257: G474-G483
- Maintenance of normal intestinal mucosa: function, structure, and adaptation.Gut. 1994; : S1-S4
- The uptake of glutamine and release of arginine, citrulline, and proline by the small intestine of developing pigs.J Nutr. 1994; 124: 2437-2444
- Oral glutamine accelerates healing of the small intestine and improves outcome after whole abdominal radiation.Arch Surg. 1990; 125: 1040-1045
- Why is epidermal growth factor present in the gut lumen?.Gut. 1995; 37: 303-305
- Oral transforming growth factor-a enhances jejunal mucosal recovery and electrical resistance in piglet rotavirus enteritis.Pediatr Res. 1995; 38: 173-181
- Glutamine modulates phenotype and stimulates proliferation in human colon cancer cell lines.Cancer Res. 1994; 22: 5974-5980
- Epidermal growth factor selectively increases maltase and sucrase activities in neonatal piglet intestine.J Physiol. 1987; 393: 583-594
- L-glutamine and transforming growth factor alpha enhance recovery of monoacylglycerol acyltransferase and diacylglycerol acyltransferase activity in porcine post-ischemic ileum.Pediatr Res. 1998; 43: 227-233
- Cytokine modulation of intestinal epithelial cell restitution: central role of transforming growth factor b.Gastroenterology. 1993; 105: 1323-1332
- Effect of glutamine and alanyl-glutamine dipeptide on mucosal proliferation of the human ileum and colon.Gastroenterology. 1994; 107: 429-434
- Absorption of epidermal growth factor occurs through the gastrointestinal tract and oral cavity in adult rats.Am J Physiol. 1995; 32: G867-G873
Article info
Publication history
Accepted:
August 10,
1998
Footnotes
☆Supported by grants from the United States Department of Agriculture (94-37204-0448) and the Center for Gastrointestinal Biology and Disease (UNC 5-32583) and by a National Research Scholarship Award from the National Institutes of Health (F32 DK09400-01) (A.T.B.).
☆☆Reprint requests: Anthony T. Blikslager, DVM, PhD, College of Veterinary Medicine, 4700 Hillsborough St, Raleigh, NC 27606.
Identification
Copyright
© 1999 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
