Overview of gastrointestinal peptides in health and disease
- Rodger A Liddle, MD
Rodger A Liddle, MD
- Professor of Medicine
- Duke University Medical School
Gastrointestinal (GI) hormones are predominantly polypeptides produced in and secreted from specialized gut endocrine cells [1,2]. These cells produce a variety of chemical transmitters that are involved in GI motility, secretion, absorption, growth, and development. Many of the peptides in the GI tract are also found in the enteric nervous system and the central nervous system.
An overview of the synthesis, secretion, and regulation of GI peptides; their role in causing disease; and their clinical application will be discussed here. The regulation and functions of the individual GI peptides are discussed separately. (See "Physiology of gastrin" and "Ghrelin" and "Pancreatic polypeptide, peptide YY, and neuropeptide Y" and "Insulin action" and "Physiology of somatostatin and its analogues" and "Physiology of cholecystokinin" and "Secretin".)
Gastrointestinal (GI) peptides are classified into families based on their primary structure (table 1). Conservation of amino acid sequence among different GI peptides suggests a common biosynthetic origin.
SYNTHESIS AND SECRETION
Synthesis — Enteroendocrine cells producing gastrointestinal (GI) peptides are dispersed throughout the GI tract. However, specific types of cells demonstrate regional specificity (table 2) . This specificity may be related to the physiologic action of the peptide and receptor location.
All GI peptides are synthesized via gene transcription of DNA into messenger RNA (mRNA) and subsequently undergo translation into precursor proteins known as preprohormones. Translation occurs on ribosomes, which are complex organelles composed of many proteins (greater than 50) and multiple large RNA molecules [4,5].
- Gut Peptides, Walsh JH, Dockray GJ (Eds), Raven Press, New York 1994.
- Physiology of the Gastrointestinal Tract, 4th ed, Johnson LR (Ed), Elsevier Academic Press, New York 2006.
- Solcia E, Fiocca R, Rindi G, et al. The pathology of the gastrointestinal endocrine system. Endocrinol Metab Clin North Am 1993; 22:795.
- Frank J. How the ribosome works. Am Sci 1998; 86:428.
- Wilson KS, Noller HF. Molecular movement inside the translational engine. Cell 1998; 92:337.
- Rothman JE, Orci L. Budding vesicles in living cells. Sci Am 1996; 274:70.
- Rehfeld JF. Processing of precursors of gastroenteropancreatic hormones: diagnostic significance. J Mol Med (Berl) 1998; 76:338.
- Bohórquez DV, Shahid RA, Erdmann A, et al. Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells. J Clin Invest 2015; 125:782.
- Chandra R, Samsa LA, Vigna SR, Liddle RA. Pseudopod-like basal cell processes in intestinal cholecystokinin cells. Cell Tissue Res 2010; 341:289.
- Bohórquez DV, Chandra R, Samsa LA, et al. Characterization of basal pseudopod-like processes in ileal and colonic PYY cells. J Mol Histol 2011; 42:3.
- Bohórquez DV, Samsa LA, Roholt A, et al. An enteroendocrine cell-enteric glia connection revealed by 3D electron microscopy. PLoS One 2014; 9:e89881.
- Wang J, Cortina G, Wu SV, et al. Mutant neurogenin-3 in congenital malabsorptive diarrhea. N Engl J Med 2006; 355:270.
- Longnecker DS. Hormones and receptors in gastrointestinal malignancies. Digestion 1990; 46 Suppl 2:92.
- Gill DM, Woolkalis MJ. Cholera toxin-catalyzed [32P]ADP-ribosylation of proteins. Methods Enzymol 1991; 195:267.
- Redfern JS, O'Dorisio TM. Therapeutic uses of gastrointestinal peptides. Endocrinol Metab Clin North Am 1993; 22:845.
- Strader AD, Woods SC. Gastrointestinal hormones and food intake. Gastroenterology 2005; 128:175.
- Wynne K, Stanley S, McGowan B, Bloom S. Appetite control. J Endocrinol 2005; 184:291.
- Yazbeck R. Teduglutide, a glucagon-like peptide-2 analog for the treatment of gastrointestinal diseases, including short bowel syndrome. Curr Opin Mol Ther 2010; 12:798.
- O'Keefe SJ, Jeppesen PB, Gilroy R, et al. Safety and efficacy of teduglutide after 52 weeks of treatment in patients with short bowel intestinal failure. Clin Gastroenterol Hepatol 2013; 11:815.
- Nauck MA. Unraveling the science of incretin biology. Am J Med 2009; 122:S3.
- Brubaker PL. Incretin-based therapies: mimetics versus protease inhibitors. Trends Endocrinol Metab 2007; 18:240.
- Imperiale TF, Birgisson S. Somatostatin or octreotide compared with H2 antagonists and placebo in the management of acute nonvariceal upper gastrointestinal hemorrhage: a meta-analysis. Ann Intern Med 1997; 127:1062.
- Karra E, Batterham RL. The role of gut hormones in the regulation of body weight and energy homeostasis. Mol Cell Endocrinol 2010; 316:120.
- Branch AD. A good antisense molecule is hard to find. Trends Biochem Sci 1998; 23:45.
- Crooke ST, Bennett CF. Progress in antisense oligonucleotide therapeutics. Annu Rev Pharmacol Toxicol 1996; 36:107.
- Bennett CF. Antisense oligonucleotides: is the glass half full or half empty? Biochem Pharmacol 1998; 55:9.