Growth factor regulation of enterocyte nutrient transport during intestinal adaptation Edward C. Ray, M.D., Nelly E. Avissar, Ph.D., Harry C. Sax, M.D., F.A.C.S* Department of Surgery, University of Rochester School of Medicine and Dentistry, Box SURG, 601 Elmwood Avenue, Rochester, NY 14642, USA Manuscript received December 17, 2001; revised manuscript January 5, 2002 Abstract Background: Intestinal adaptation occurs in response to injury or alteration in nutrient availability. It is both morphologic and physiologic in nature and can be mediated by growth factors and nutrients. Pathologic conditions such as short-bowel syndrome and inflammatory bowel disease lead to derangements in nutrient absorption that may exceed the body’s regenerative and adaptive capacity. Failure to fully adapt often results in long-term dependence on parenteral nutrition, leading to decreased quality of life and excessive medical expenses. The therapeutic use of appropriate growth factors may increase the adaptive capabilities of the gut. Data Source: Medline and current literature review. Conclusions: The major known nutrient transporters present in the gut and the mechanisms by which growth factors alter transport activity during intestinal adaptation are summarized. Growth factors have the potential to improve nutrient absorption in some bowel diseases. © 2002 Excerpta Medica, Inc. All rights reserved. Keywords: Growth factors; Enterocyte; Amino acid transport; Oligopeptide transport; Intestinal adaptation; Brush-border membrane Abbreviations AAT: amino acid transporter BBM: brush-border membrane BLM: basolateral membrane DAG: diacylglycerol EGF: epidermal growth factor EGFR: epidermal growth factor receptor FABP: fatty acid binding protein FAT: fatty acid transporter FFA: free fatty acids FGF: fibroblast growth factor GHR: growth hormone receptor GLP: glucagon-like peptide GLUT: glucose transporter HGF: hepatocyte growth factor HGH: human growth hormone IGF: insulin-like growth factor IGFBP: insulin-like growth factor binding proteins IP 3 : inositol 1,4,5 triphosphate Jak: Janus kinase KGF: keratinocyte growth factor MAP kinase: mitogen-activated protein kinase NEC: necrotizing enterocolitis PepT-1: oligopeptide transporter PI-3 kinase: phosphatidyl inositol-3 kinase PKC: protein kinase C PLC: phospholipase C STAT: signal transducer of activated transcription SBS: short bowel syndrome SGLT: sodium-glucose cotransporter TGF: transforming growth factor  TKR: tyrosine kinase receptor Overview of enterocyte nutrient absorption Intestinal epithelium is one of the most metabolically active tissues in the body. Beginning as immature crypt cells, enterocytes differentiate and migrate up the crypt- villus axis over a period of 2– 4 days, eventually to be removed by apoptosis. In response to mucosal injury, mal- nutrition, or loss of absorptive surface area, enterocytes demonstrate accelerated growth and altered nutrient trans- port activity by an intricate process termed adaptation [1]. * Corresponding author. Tel: +1-585-273-1428; fax: +1-585-273- 1252. E-mail address: Harry_Sax@urmc.rochester.edu The American Journal of Surgery 183 (2002) 361–371 0002-9610/02/$ – see front matter © 2002 Excerpta Medica, Inc. All rights reserved. PII: S0002-9610(02)00805-X