Effect of subcutaneous insulin on intestinal adaptation in a rat model of short bowel syndrome

Pediatric Surgery International - 2004
Igor Sukhotnik1, Jorge Mogilner1, Raanan Shamir2, Naim Shehadeh2, Jacob Bejar1, Mark Hirsh2, Arnold G. Coran3
1Department of Pediatric Surgery B, Rappaport Faculty of Medicine, Technion, Bnai Zion Medical Center, Haifa, Israel
2Rambam Medical Center, Haifa, Israel
3Section of Pediatric Surgery, Mott Children’s Hospital, University of Michigan, Ann Arbor, USA

Tóm tắt

Insulin has been shown to influence intestinal structure and absorptive function. The purpose of the present study was to evaluate the effects of parenteral insulin on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: sham rats underwent bowel transection and reanastomosis, SBS rats underwent a 75% small bowel resection, and SBS-INS rats underwent a 75% small bowel resection and were treated with insulin given subcutaneously at a dose of 1 U/kg, twice daily, from day 3 through day 14. Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 15 following operation. SBS rats demonstrated a significant increase in jejunal and ileal bowel and mucosal weight, villus height and crypt depth, and cell proliferation index compared with the sham group. SBS-INS animals demonstrated higher jejunal and ileal bowel and mucosal weights, jejunal and ileal mucosal DNA and protein, and jejunal and ileal crypt depth compared with SBS animals. SBS-INS rats also had a greater cell proliferation index in both jejunum and ileum and a trend toward a decrease in enterocyte apoptotic index in jejunum and ileum compared with the SBS untreated group. In conclusion, parenteral insulin stimulates structural intestinal adaptation in a rat model of SBS. Increased cell proliferation is the main mechanism responsible for increased cell mass.

Từ khóa


Tài liệu tham khảo

Booth IW, Lander AD (1998) Short bowel syndrome. Baillieres Clin Gastroenterol 12:739–772

Coran AG, Spivak D, Teitelbaum DH (1999) An analysis of the morbidity and mortality of short bowel syndrome in the pediatric age group. Eur J Pediatr Surg 9:228–230

O’Brien DP, Nelson LA, Huang FS, et al. (2001) Intestinal adaptation: structure, function, and regulation. Semin Pediatr Surg 10:55–64

Thiesen A, Drozdowski L, Iordache C, et al. (2003) Adaptation following intestinal resection: mechanisms and signals. Best Pract Res Clin Gastroenterol 17:981–995

Podolsky DK (1994) Peptide growth factors in the gastrointestinal tract. In: Johnson LR (ed) Physiology of the gastrointestinal tract, 3rd edn. Raven Press, New York, pp 129–167

Laburthe M, Rouyer-Fessard C, Gammeltoft S (1988) Receptors for insulin-like growth factors I and II in rat gastrointestinal epithelium. Am J Physiol 254:G457–G462

Olanrewaju H, Patel L, Seidel ER (1992) Trophic action of local intraileal infusion of insulin-like growth factor I: polyamine dependence. Am J Physiol 263:E282–E286

Lund PK (1998) Molecular basis of intestinal adaptation: the role of the insulin-like growth factor system. Ann N Y Acad Sci 859:18–36

Ziegler TR, Mantell MP, Chow JC, et al. (1996) Gut adaptation and the insulin-like growth factor system: regulation by glutamine and IGF-1 administration. Am J Physiol 271:G866–G875

Dowling RH, Booth CC (1967) Structural and functional changes following small intestinal resection in the rats. Clin Sci 32:139–149

Chomszynski P (1993) A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. Biotechniques 15:532–536

Lund PK (1994) Insulin-like growth factors. In: Dockray G, Walsh JH (eds) Gut peptides: biochemistry and physiology. Raven Press, New York, pp 587–613

Lund PK, Moats-Staats BM, Hynes MA, et al. (1986) Somatomedin-C/insulin-like growth factor-I and insulin-like growth factor-II mRNAs in rat fetal and adult tissues. J Biol Chem 261:14539–14544

Han VK, Lund PK, Lee DC, et al. (1988) Expression of somatomedin/insulin-like growth factor messenger ribonucleic acids in the human fetus: identification, characterization, and tissue distribution. J Clin Endocrinol Metab 66:422–429

Vanderhoof JA, McCusker RH, Clark R, et al. (1992) Truncated and native insulinlike growth factor I enhance mucosal adaptation after jejunoileal resection. Gastroenterology 102:1949–1956

Kojima H, Hidaka H, Matsumura K, et al. (1998) Concerted regulation of early enterocyte differentiation by insulin-like growth factor I, insulin, and transforming growth factor-beta1. Proc Assoc Am Physicians 110:197–206

Georgiev IP, Georgieva TM, Pfaffl M, et al. (2003) Insulin-like growth factor and insulin receptors in intestinal mucosa of neonatal calves. J Endocrinol 176:121–132

Shulman RJ (1990) Oral insulin increases small intestinal mass and disaccharidase activity in the newborn miniature pig. Pediatr Res 28:171–175

Arsenault P, Menard D (1984) Insulin influences the maturation and proliferation of suckling mouse intestinal mucosa in serum free organ culture. Biol Neonate 46:229–236

Buts JP, de Kayser N, Dive C (1988) Intestinal development in the suckling rat: effect of insulin on the maturation of villous and crypt functions. Eur J Clin Invest 18:391–398

Sukhotnik I, Yakirevich E, Coran AG, et al. (2002) Transforming growth factor-alpha increases enterocyte proliferation, decreases apoptosis and stimulates intestinal adaptation in a rat model of short bowel syndrome. J Surg Res 108:235–242

Sukhotnik I, Mor-Vaknin N, Drongowski RA, et al. (2004) Effect of dietary fat on early morphological intestinal adaptation in a rat with short bowel syndrome. Pediatr Surg Int 20(4):235–239

Thông tin
Thông tin xuất bản

Pediatric Surgery International

Thông tin tác giả