TY - JOUR
T1 - Actions and therapeutic pathways of ghrelin for gastrointestinal disorders
AU - Camilleri, Michael
AU - Papathanasopoulos, Athanasios
AU - Odunsi, Suwebatu T.
N1 - Funding Information:
M. Camilleri is funded in part by grants rO1-DK54681, rO1-DK67071 and K24-DK02638 from the NiH. A. Papathanasopoulos is funded by an international grant of the Hellenic society of Gastroenterology.
PY - 2009
Y1 - 2009
N2 - Ghrelin is a peptide hormone that possesses unique orexigenic properties. By acting on the growth-hormone secretagogue receptor 1a, ghrelin induces a short-term increase in food consumption, which ultimately induces a positive energy balance and increases fat deposition. Reduced ghrelin levels have been observed in obese patients and after bariatric surgery. In particular, bariatric procedures that involve gastric resection or bypass lead to reduced ghrelin levels. Administration of physiological doses of exogenous ghrelin to humans does not significantly alter gastric motility; however, administration of high doses stimulates gastric motility, with increased gastric tone and emptying, and increased activity of migrating motor complexes in the small bowel. The potential of ghrelin agonists to be used as prokinetics is being tested in patients with gastroparesis and postoperative ileus. Ghrelin acts directly on pancreatic islet cells to reduce insulin production. Findings from studies in animals have revealed that small-molecule ghrelin antagonists favorably influence glucose tolerance, appetite suppression and weight loss. Other studies have demonstrated that ghrelin antagonists retard gastric emptying only at very high doses, which suggests that these agents will probably not induce upper gastrointestinal symptoms. The potential of this new class of therapeutic agents to influence appetite and glycemic control strongly indicates that they should be tested in clinical trials.
AB - Ghrelin is a peptide hormone that possesses unique orexigenic properties. By acting on the growth-hormone secretagogue receptor 1a, ghrelin induces a short-term increase in food consumption, which ultimately induces a positive energy balance and increases fat deposition. Reduced ghrelin levels have been observed in obese patients and after bariatric surgery. In particular, bariatric procedures that involve gastric resection or bypass lead to reduced ghrelin levels. Administration of physiological doses of exogenous ghrelin to humans does not significantly alter gastric motility; however, administration of high doses stimulates gastric motility, with increased gastric tone and emptying, and increased activity of migrating motor complexes in the small bowel. The potential of ghrelin agonists to be used as prokinetics is being tested in patients with gastroparesis and postoperative ileus. Ghrelin acts directly on pancreatic islet cells to reduce insulin production. Findings from studies in animals have revealed that small-molecule ghrelin antagonists favorably influence glucose tolerance, appetite suppression and weight loss. Other studies have demonstrated that ghrelin antagonists retard gastric emptying only at very high doses, which suggests that these agents will probably not induce upper gastrointestinal symptoms. The potential of this new class of therapeutic agents to influence appetite and glycemic control strongly indicates that they should be tested in clinical trials.
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U2 - 10.1038/nrgastro.2009.72
DO - 10.1038/nrgastro.2009.72
M3 - Review article
C2 - 19434096
AN - SCOPUS:67149136168
SN - 1759-5045
VL - 6
SP - 343
EP - 352
JO - Nature Reviews Gastroenterology and Hepatology
JF - Nature Reviews Gastroenterology and Hepatology
IS - 6
ER -