The use of ghrelin and ghrelin receptor agonists as a treatment for animal models of disease: efficacy and mechanism.
Ghrelin is a stomach-derived hormone that acts at the ghrelin receptor (formerly called the Growth Hormone Secretagogue (GHS)-1a receptor) in multiple tissues throughout the body, exhibiting pleotropic effects potentially beneficial as a treatment in human disease states. Given its properties including increasing appetite, decreasing systemic inflammation, decreasing vascular resistance, increasing cardiac output, and increasing growth hormone and IGF-1 levels, ghrelin has been tested as a treatment in animal models of multiple disease states that produce the deficits in these processes. Thus, the efficacy of ghrelin has been testing in diseases involving anorexia, negative energy balance, cardiovascular compromise, systemic inflammation and gastroparesis. These diseases include cancer cachexia, chronic heart failure, chronic renal failure, chemotherapy, arthritis, gastroparesis and inflammatory bowel disease. Across this wide variety of diseases treatment with ghrelin and ghrelin agonists have produced benefits, though given ghrelin's widespread effects, the exact mechanisms behind ghrelin's action in these settings is frequently difficult to determine. Further investigation using animal models may help to determine mechanisms that are most operative in these disease states and narrow treatment parameters helpful for human application.
Department of Pediatrics, Division of Pediatric Endocrinology, University of Virginia, P.O. Box 800386, Charlottesville, VA 22908, USA. deboer@virginia.edu
Mark D
MD
DeBoer
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001069:Appetite Regulation / Q000187:drug effects*; D019167:Appetite Stimulants / Q000494:pharmacology / Q000627:therapeutic use*; D002100:Cachexia / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000627:therapeutic use; D004195:Disease Models, Animal; D054439:Ghrelin / Q000819:agonists* / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D054440:Receptors, Ghrelin / Q000819:agonists* / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000276:immunology / Q000503:physiopathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D019167:Appetite Stimulants; D002316:Cardiotonic Agents; D054439:Ghrelin; D054440:Receptors, Ghrelin